all Flashcards
Non-Proliferative Diabetic Retinopathy (NPDR)
Other Diagnoses to Consider
• Retinal vein occlusion
• Hypertensive retinopathy
• Ocular ischaemic syndrome
• Radiation retinopathy
Risk Factors for Diabetic Retinopathy (DR)
The Royal College of Ophthalmologists (RCOphth) Diabetic Retinopathy Guidelines 2012
• Non-modifiable
– Genetic factors
– Gender
– Duration of diabetes
• Modifiable
– Glycaemia – BP
– Lipid levels
• Other
– Carotid arterial disease
– Pregnancy
– Renal impairment
– Smoking
Classification
• Proposed International Clinical Diabetic Retinopathy Severity Scale 2003
– Mild NPDR:
Microaneurysms (MAs) only
– Moderate NPDR:
More than just MA’ but less than severe NPDR
– Severe NPDR (4-2-1 rule) — one or more of the following features are present:
More than 20 intraretinal haemorrhages in each of 4 quadrants
Definite venous beading in 2 or more
quadrants
Prominent intraretinal microvascular
abnormalities (IRMA) in 1 or more
quadrants
– Very severe NPDR:
Two or more features of severe NPDR are present
Public Health England NHS Diabetic Eye Screening Programme Grading Definitions 2017
– R0: No retinopathy
– R1 (Background DR/mild NPDR): Venous loop
Microaneurysms
Retinal haemorrhage
Any exudate or cotton wool spot in pres- ence of other non-referable DR features
– R2 (pre-proliferative DR/moderate NPDR):
Venous beading
Venous reduplication
Multiple blot haemorrhages (if uncertain,
refer only in the presence of IRMA that
are definitely seen)
• Blot haemorrhages (located in OPL and
INL) are larger than the width of the smallest of the four branches of the cen- tral retinal vein as it crosses the edge of the disc
IRMA (check that they can still be seen on the colour image as well as the red-free image that has not been enlarged)
Examination
• Microaneurysms (MAs): small red dots
• Intraretinal haemorrhages: dot and blot haemorrhages, flame haemorrhages
• Hard exudates: sharply demarcated yellow-
white deposits within the retina
• Cotton wool spots (CWS — patches of relative ischaemia affecting the NFL of the retina): small white patches with wispy borders situated in the inner retina
• Venous beading: localised areas of change in vessel calibre with alternating regions of relative dilation and constriction
• Venous loops
• Intraretinal microvascular abnormalities
(IRMA): segments of dilated and tortuous retinal vasculature without crossing both arterioles or veins in the underlying retina
• Subretinal fibrosis
Investigations
• Blood test for diagnosis of diabetes mellitus: – Venous fasting glucose ≥7.0 mmol/L
and/or
– Oral glucose tolerance test (75 g anhydrous glucose) with a 2-h value ≥11.1 mmol/L and/or
– Random venous glucose ≥11.1 mmol/L
• FFA:
– MAs appear as hyperfluorescent dots
visible during the arteriovenous transit
phase
– Intraretinal haemorrhages appear hypofluorescent blocking normal fluorescence from the underlying choroid
– Exudates appear hypofluorescent
– CWS appear hypofluorescent
– IRMA appear hyperfluorescent during the arteriovenous transit phase and are often situated at the borders of areas of capillary non-perfusion
Treatment
Modification of life-style:
– Smoking cessation
– Weight loss
– Exercise
Modification of systemic risk factors:
– Hyperglycaemia control:
DCCT (The Diabetes Control and Complications Trial Research Group
1995): Type 1 DM — tight control of HbA1C at mean of 7.2% was associated with 76% reduction in onset of retinopathy and slowed progression of DR by 54%, 60% reduction in onset of neuropathy, and 54% reduction in onset of nephropathy at 6.5 years
UKPDS (UK Prospective Diabetes Study Group 1998): Type 2 DM — tight control of HbA1C at mean of 7% was associated with a 25% reduction in the onset of micro- vascular disease ACCORD (The ACCORD Study Group and ACCORD Eye Study Group 2010): Type 2 DM — intensive control of HbA1C reduced progression of DR by 42% and reduced development of PDR from 10.2% to 6.5%: avoid Pioglitazone in the presence of macular oedema, personalized HbA1C target should be set, usually between 48–58 mmol/mol (6.5–7.5%)
– BP control:
UKPDS (UK Prospective Diabetes Study Group 1998): Type 2 DM — tight control of BP at mean of 144/82 was associated with a 37% reduction in the onset of micro- vascular disease and 32% reduction in dia- betes related deaths
– Lipid control:
ACCORD (The ACCORD Study Group and ACCORD Eye Study Group 2010): Type 2 DM — 40% reduction in the odds of having progression of DR over 4 years in patients allocated to fenofibrate in combi- nation with a statin, compared to simvas- tatin alone): consider adding fenofibrate to a statin for NPDR in type 2 DM, avoid statins in pregnancy
Follow-Up
• Mild NPDR: discharge to community for DRSS screening or 12 months follow up if seen in hospital eye service
• Moderate NPDR: 3–6 months
• Severe NPDR: less than 3 months
Prognosis
• In the Diabetic Retinopathy Study (DRS) (The Diabetic Retinopathy Study Research Group 1981), 50% of untreated severe DR will develop proliferative diabetic retinopathy (PDR) within 15 months
• In the Early Treatment Diabetic Retinopathy Study (ETDRS) (Early Treatment Diabetic Retinopathy Study Research Group. ETDRS report number 12. 1991b):
– 6.2% risk of progression to PDR at 1 year for mild NPDR
– 11.3% risk of progression to PDR at 1 year for moderate NPDR
– 20.7% risk of progression to PDR at 1 year for severe NPDR
Diabetic Macular Oedema (DMO)
Other Causes of Macular Oedema to Consider
• Inflammatory disorders: post-operative (cataract, VR, corneal), post-laser (PI, PRP), post- cryotherapy, uveitis
• Retinal vascular diseases: DR, RVO, OIS, hypertensive retinopathy, radiation retinopathy, MacTel
• Choroidal vascular disease: CNV
• Drugs: latanoprost, topical adrenaline, glitazones, niacin, chemotherapy agents (e.g.
paclitaxel)
• Inherited retinal dystrophies: RP, autosomal dominantly inherited CMO
• Disorders of vitreoretinal interface: VMT,
ERM
• Optic nerve head abnormalities: optic disc pit, optic disc coloboma
• Tumours of the choroid/retina
Classification
• Proposed International Clinical Diabetic Macular Edema Severity Scale, 2003
– Mild DME:
Some retinal thickening or exudates in the posterior pole, distant from the center of the macula
– Moderate DME:
Retinal thickening or exudates near the center of the macula but not involving the center
– Severe DME:
Retinal thickening or exudates involving the center of the macula
• Public Health England NHS Diabetic Eye Screening Programme Grading Definitions 2017
– M0: No maculopathy
– M1:Exudate within 1 DD of the centre of the fovea
Circinate or group of exudates within the macula:
• A group of exudates is an area of exu-
dates that is greater than or equal to half the disc area and this area is all within the macular area
• To work out the area, the outer points of the exudates are joined and compared to half the area of the optic disc
• Any MA or haemorrhage within 1 DD of the centre of the fovea only if associ- ated with a best VA of 6/12 or worse
Examination
• Exudates within the macula
• MAs or retinal haemorrhages within the
macula
• Clinically significant macular oedema —
CSMO (Early Treatment Diabetic Retinopathy Study Research Group. ETDRS report num- ber 9. 1991a):
– Retinal thickening at or within 500 μm of
the centre of the macula and/or
– Exudates at or within 500 μm of the centre
of the macula, if associated with thickening
of the adjacent retina and/or
– Zone or zones of retinal thickening 1-disc area or larger, any part of which is within 1 DD of the center of the macula
Investigations
•OCT
– Exudates appear as hyperreflective foci
within the retina
– Macular oedema
– Traction from ERM or VMT causing
underlying macular oedema in the absence of retinal vascular leakage demonstrable by FFA
FFA
– Petaloid pattern of leakage from macular
oedema
– Enlarged foveal avascular zone from ischaemic diabetic maculopathy
Treatment
• Focal/grid laser
– ETDRS (Early Treatment Diabetic
Retinopathy Study Research Group. ETDRS report number 9. 1991a): focal/ grid laser reduced the risk of moderate vision loss (loss of ≥15 letters from baseline) by 50% at 3 years in eyes with mild or moderate NPDR with CSMO
– Indicated if CMT <400 μm and CSMO is not center involving (RCOphth Diabetic Retinopathy Guidelines 2012)
• Anti-VEGF therapy
– Aflibercept (Eylea)
NICE Guidance [TA346]: option for treat- ment of DMO if CMT ≥400 μm at the start of treatment
Regimen: a single injection every month for 5 consecutive months, followed by one injection every 2 months with no require- ment for monitoring between visits for the first 12 months
Clinical trials:
• VISTA study (Brown et al. 2015)
• VIVID study (Brown et al. 2015)
– Ranibizumab (Lucentis)
NICE Guidance [TA274]: option for treatment of DMO if CMT ≥400 μm at the start of treatment
Regimen: given monthly and continued until maximum VA is reached — VA stable for 3 consecutive months:
Clinical trials:
• RISE study (Nguyen et al. 2012; Brown et al. 2013)
• RIDE study (Nguyen et al. 2012; Brown et al. 2013)
• RESTORE study (Mitchell et al. 2011)
• Dexamethasone implant (Ozurdex)
– NICE Guidance [TA349]: option for treat- ment of DMO if eye is pseudophakic and CSMO does not respond to non-corticoste- roid treatment or such treatment is unsuitable
– Regimen: A single implant is injected into the vitreous and remains in the vitreous for up to 270 days before fully dissolving
– Clinical trials:
MEAD study (Boyer et al. 2014) BEVORDEX study (Gillies et al. 2014) PLACID study (Callanan et al. 2013)
• Fluocinolone implant (Iluvien)
– NICE Guidance [TA301]: option for the
treatment of chronic CSMO that is insuffi- ciently responsive to available therapies if an eye is pseudophakic
– Regimen: A single 190 μm of Fluocinolone Acetonide implant is injected with daily release of 0.2 μg/day for 36 months
– Clinical trials:
FAME study (Cunha-Vaz et al. 2014)
3.2.6 Follow-Up
• Center involved DMO: 1–3 months
• Non-center involved DMO: 3–6 months
• Stable treated DMO: 3–6 months
Focal and Grid Laser Techniques
Diabetic Retinopathy Clinical Research Network (DRCR.net) laser techniques (Writing Committee for the Diabetic Retinopathy Clinical Research Network et al. 2007)
• Focal treatment
– Topical anaesthetic
– Spot size: 50 μm
– Burn duration: 0.05–0.1 s
– Burn intensity: mild grey-white burn evi-
dent beneath all MAs
– Directly treat all leaking MA’s in areas of
retinal thickening between 500 and
3000 μm from the center of the macula – Follow up: 3–4 months
• Grid treatment
– Topical anaesthetic
– Spot size: 50 μm
– Burn duration: 0.05–0.1 s
– Burn intensity: light grey burn
– Burn separation: two visible burn widths
apart
– Apply to all areas with oedema not associated with MA’s: 500–3000 μm superiorly, nasally and inferiorly from center of mac- ula; 500–3500 μm temporally from macu- lar center; no burns placed within 500 μm of optic disc
– Follow up: 3–4 months
–Complications: pain, worsened VA, choroidal detachment or RD, CNV membrane, vitreous haemorrhage
Proliferative Diabetic Retinopathy (PDR)
Other Causes of Neovascularisation to Consider
• Retinal vein occlusion
• Ocular ischaemic syndrome
• Radiation retinopathy
• Occlusive retinal vasculitis — MS, sarcoid, Behcet’s disease
High-Risk PDR
• Defined by the Diabetic Retinopathy Study (The Diabetic Retinopathy Study Research Group 1981) with patients at higher risk of visual loss and requires prompt PRP treatment
– Neovascularisation of the disc (NVD — new vessels on or within 1 DD of the optic disc): NVD ≥1/4 disc area or any size NVD with vitreous and/or pre-retinal haemorrhage
– Neovascularisation elsewhere in the retina (NVE): NVE ≥1/2 disc area with vitreous and/or pre-retinal haemorrhage
PDR in Pregnancy
NICE Guidance [NG3]
• Diabetic patients planning pregnancy should be informed on the need for assessment of DR before and during pregnancy
• Statins and drugs blocking the renin-angiotensin system should be discontinued before conception and always at first antenatal booking if still being taken
• Ideally, all patients with PDR should be identified and treated prior to conception
• Rapid optimisation of poor glycaemic control should be deferred at least until after retinal assessment
• Retinal assessment during and after pregnancy:
– Newly pregnant women with pre-existing DM should be offered retinal assessment by digital imaging following their first antenatal clinic (i.e. first trimester, typically 8–12 weeks) appointment (unless they have had a retinal assessment in the last 3 months) and again at 28 weeks (third trimester) if the first assessment is normal. If any DR is present, an additional retinal assessment should be performed at 16–20 weeks (second trimester)
– At term, DR should not be considered a contraindication to vaginal birth
– Women who have NPDR diagnosed during pregnancy should have ophthalmological follow up for at least 6 months following the birth of the baby
– Tropicamide alone should be used if mydriasis is required during pregnancy
• Women with gestational DM are not at increased risk for the development of DR and do not need such monitoring.
Treatment
• Modification of life-style
• Modification of systemic risk factors
• Pan-retinal photocoagulation (PRP)
– Indications (The Royal College of Ophthalmologists Diabetic Retinopathy Guideline 2012): presence of NVD/NVE/ NVI/NVA — PRP performed on same day
or within 2 weeks of diagnosis, consider PRP for severe/very severe NPDR in older • patients with type 2 DM, where retinal view is difficult, prior to cataract surgery,
in only eye where first eye lost to PDR, where regular clinic attendance is likely to be poor, difficult to examine patient for other reasons
– Prognosis (The Diabetic Retinopathy Study Research Group 1981): PRP reduces severe vision loss (<5/200 at two consecutive visits) from high risk PDR by 50% at
2 years
• Vitrectomy
– Indications (The Royal College of Ophthalmologists Diabetic Retinopathy Guideline 2012): non-clearing (within 3 months for type 2 diabetic and 1 month
for a type 1 diabetic) severe vitreous haemorrhage (confirmation of attached retina not possible with ophthalmoscopic examination), significant recurrent vitreous haemorrhage despite maximal PRP, tractional RD involving or threatening the fovea, combined tractional rhegmatogenous RD which involves or threatens to involve the fovea, diffuse CSMO associated with posterior hyaloidal traction
– Prognosis (The Diabetic Retinopathy Vitrectomy Study Research Group 1988): early vitrectomy (for those with severe vitreous haemorrhage with VA 5/200 or worse) increased chance of 20/40 vision from 12% to 36% in type 1 diabetics
Prognosis
• 25% with type 1 DM and 16% with type 2 DM will develop PDR after 15 years of DM (Klein et al. 1984)
PRP Laser Technique
RCOphth Diabetic Retinopathy Guideline
•Topical anaesthetic
•Spot size: 400 μm spot size (if 200 μm is preselected on laser interface, a Mainster 165 PRP lens with a spot magnification factor of 1.96 will produce a theoretical retinal spot size of 392 μm. If other fundus lens is selected, it is expected that appropriate adjustments will be made to spot size selection)
•Burn duration: 20 ms
•Burn intensity: barely visible grey-white burn (titrate power down by up to 50 mW in the periphery)
•Burn separation: 1 visible burn width apart for early or moderate PDR, 0.5 burn width apart for severe PDR
•Retinal surface coverage: burns applied as far peripheral as possible up to the ora serrata, no closer than 3000 μm temporal to fovea, no closer than 500 μm nasal to the optic disc, no further posterior than one burn within the temporal arcades
•No. of sessions to complete full primary PRP: 1–2 sessions within 2 weeks for mild (NVD or NVE <1/3 disc area and flat) and moderate (NVD or NVE >1/3 disc area) PDR, 2–3 sessions in 3–4 weeks for severe (NVD or NVE with tractional RD) PDR, 3–4 sessions within 4 weeks for young patients with type 1 diabetes with PDR (increased risk of developing macular oedema post PRP)
•Follow up: 4 months for early PDR, 3 months for moderate PDR, 2 weeks for PDR in preg-nancy. Regression of new vessels is characterised by blunting of the NV growing tips or replacement with fibrosis
• Complications:
– Related to damage to posterior ocular
structures:
Retinal tear
Choroidal haemorrhage
Choroidal neovascularisation
Vitreous, pre-retinal or subhyaloid haemorrhage
Inadvertent optic disc or foveal damage Related to loss of visual function: Diminished or loss of peripheral visual field — implications for driving
Diminished colour vision and contrast sensitivity
Reduced or loss of dark adaptation —
effect on night vision
Related to the destructive nature of the procedure:
Pain during and shortly after treatment Corneal epithelial defects and recurrent erosions
Mydriasis
Iris burns and damage/lenticular burns or opacification
Related to contraction of fibrovascular tissue:
Progressive traction RD
Related to break down of blood-retinal bar- rier breakdown:
Exudative RD/choroidal detachment/cho- roidal effusion
Macular oedema
Branch Retinal Vein Occlusion (BRVO)
Other Diagnoses to Consider
• Macular telangiectasia
• Diabetic retinopathy
• Radiation retinopathy
• Susac syndrome: small BRAO (may be multiple) and capillary occlusions, sensorineural hearing loss, subacute encephalopathy, hyperintense lesions in the corpus callosum on T2 MRI
• Behcet’s disease • Sarcoidosis
3.4.2 Risk Factors
• Arteriosclerosis: HTN, DM, smoking, hyper- lipidaemia (including secondary to hypothyroidism)
• Glaucoma
• Ocular inflammatory disease: Behcet’s disease, PAN, sarcoidosis, SLE
• Haematological: Protein C, protein S or antithrombin deficiency, activated protein C resistance, factor V Leiden, myeloma, Waldenstrom’s macroglobulinaemia, antiphospholipid syndrome
Examination
• Acute BRVO: wedge shaped segmental distribution of intraretinal haemorrhage in a quadrant of the fundus, narrowed branch retinal vein passing under a retinal artery, dilated and tortuous retinal vein, cotton wool spots
• Chronic BRVO: telangiectatic vessels (dila- tion of capillaries) forming collaterals that cross the horizontal raphe, microaneurysms, exudates, sclerosed retinal vein ±NVE > NVD > NVI
• Check for RAPD
• Check the IOP
• Look for NVI on anterior segment
examination
• Perform gonioscopy for NVA
Investigations
RCOphth Retinal Vein Occlusion (RVO) Guidelines 2015
• BP
• Bloods: FBC, ESR, glucose
• OCT: CMO
• FFA (if uncertain diagnosis): delayed filling of
the occluded retinal vein, capillary non-perfusion — >5 DD is defined as an ischaemic BRVO (The Branch Vein Occlusion Study Group 1984, 1986), macular ischaemia, telan- giectatic vessels forming collaterals that cross the horizontal raphe
Treatment
• Control of cardiovascular risk factors: HTN, hyperlipidaemia, smoking, DM
• Neovascularisation: sectoral PRP — branch vein occlusion study — BVOS (The Branch Vein Occlusion Study Group 1984, 1986) rec- ommended that laser photocoagulation be applied only after NV is observed, which reduces the likelihood of vitreous haemor- rhage from about 60% to 30%
• Macular oedema:
– Laser photocoagulation
BVOS (The Branch Vein Occlusion Study Group 1984, 1986):
• An RCT that aimed to answer three
questions: (1) can laser photocoagula- tion improve VA compared to observa- tion in eyes with macular oedema from BRVO that reduces the vision to 6/12 or worse; (2) can sectoral PRP prevent the development of NV; (3) can sectoral PRP prevent vitreous haemorrhage
• Wait for at least 3 months if VA 6/12 or worse before considering laser therapy to allow clearing of intraretinal haemor- rhages to permit FFA and evaluation of macular oedema and macular ischaemia
• If perfused macular oedema accounts for the visual loss, and vision continues
to be 6/12 or worse without spontaneous improvement, consider grid macular photocoagulation (0.1 s duration, 100 μm spot size, power titrated to pro- duce a “medium” white burn) to the leaking area demonstrated by FFA
• After 3 years of follow-up, 65% of treated eyes gained two or more lines of vision compared to 37% of untreated eyes
– Dexamethasone implant (Ozurdex)
NICE Guidance [TA229]: recommend as an option for treatment of macular oedema due to a BRVO when treatment with laser photocoagulation has not been beneficial or treatment with laser photocoagulation is not considered suitable because of the extent of retinal haemorrhages
GENEVA study (Haller et al. 2010): A RCT that evaluated the effects of a single dexa- methasone implant compared to sham injection for the treatment of macular oedema secondary to BRVO and CRVO. Increase in BCVA of ≥15 ETDRS letters was achieved in 30% of the Ozurdex 0.7 mg group, 26% of the Ozurdex 0.35 mg group, and 13% of the sham group 60 days after injection (peak response) and was maintained through day 90 in BRVO patients. There was no differ- ence between either Ozurdex groups and the sham group at day 180.
– Ranibizumab (Lucentis)
NICE Guidance [TA283]: recommend as an option for treatment of macular oedema due to a BRVO when treatment with laser photocoagulation has not been beneficial or treatment with laser photocoagulation is not considered suitable because of the extent of retinal haemorrhages
BRAVO study (Campochiaro et al. 2010): A RCT to evaluate the efficacy and safety of Lucentis in the treatment of macular oedema from BRVO. Patients were randomised into three groups:(1)sham injection;(2)0.3mg Lucentis; and (3) 0.5 mg Lucentis. In the first 6 months, injections were given monthly. At 6 months, both Lucentis groups gained +16.6 and +18.3 ETDRS letters (0.3 and 0.5 mg groups, respectively) com- pared with a gain of +7.3 letters in the control group. At 6 months, 55.2% and 61.1% of patients receiving Lucentis 0.3 and 0.5 mg gained ≥3 ETDRS lines compared to 28.8% in the sham injection group Aflibercept (Eylea)
NICE Guidance [TA305]: recommend as an option for treatment of visual impair- ment caused by macular oedema following BRVO
VIBRANT study (Campochiaro et al. 2015): A RCT that evaluated the efficacy and safety of Eylea compared to macular grid laser in the treatment of macular oedema from BRVO or HRVO. After 6 months of treat- ment, 26.7% of the laser group gained ≥3 ETDRS lines compared to 52.7% in the Eylea group. Mean change in letters from baseline was +6.9 letters in the laser group compared to +17.0 letters in the Eylea group
RCOphth RVO Guidelines 2015 Treatment Algorithm
Non-ischaemic BRVO
• Baseline
– If VA better than 6/12, it is reasonable to
regularly observe progress for 3 months
– If VA is 6/12 or worse with macular oedema and haemorrhages that are not masking fovea:
FFA is recommended to assess foveal integrity
If no macular ischaemia is identified, regu- larly observe for 3 months if macular oedema is mild and in opinion of clinician likely to spontaneously improve (30% chance)
If mild to moderate macular ischaemia is present consider treatment with ranibizumab or dexamethasone implant (Ozurdex) if spontaneous improvement is unlikely
If severe macular ischaemia is present — no treatment is recommended and regularly observe for NV formation
– If VA is 6/12 or worse with macular oedema and haemorrhages that are masking fovea: Monthly ranibizumab or baseline dexamethasone implant (Ozurdex) for 3 months Perform FFA at 3 months to assess foveal integrity
If severe macular ischaemia is found to be present at 3 months, no treatment will likely be beneficial and further therapy should be carefully considered
• At 3 months follow up
– Consider modified grid laser photocoagulation if persistent macular oedema, no or minimal macular ischaemia and other treatments unsuccessful or unavailable
– If VA 6/9 or better or no macular oedema detected, continue to observe if initially observed. If on anti-VEGF or dexamethasone implant (Ozurdex) therapy, continue as suggested in macular oedema due to CRVO
• Further follow up:
– If under observation only, follow up 3
monthly intervals for 18 months
– In case of recurrence or new macular oedema, consider re-initiating intravitreal ranibizumab or dexamethasone implant
(Ozurdex) therapy
Ischaemic BRVO
• Watch carefully for NV
• If NVE: consider sector laser PRP applied to all ischaemic quadrants ± off license bevacizumab (Avastin)
• Follow up at 3 monthly intervals for up to
24 months
Prognosis
• BVOS (The Branch Vein Occlusion Study Group 1984, 1986):
– Only eyes with ischaemic BRVO (>5 DD
of retinal capillary non-perfusion) are at risk of developing NV — 40% of these eyes develop NV, and of these 40%, 60% will experience periodic vitreous haemorrhage
- Retinal or disc NV, or both, may develop at any time within the first 3 years after an occlusion but are most likely to appear within the first 6-12months after the occlusion
Up to 10% of patients with BRVO in one eye will develop any type of RVO in the fellow eye
Central Retinal Vein Occlusion (CRVO)
Other Diagnoses to Consider
• Diabetic retinopathy
• Ocular ischaemic syndrome
• Radiation retinopathy
• Hypertensive retinopathy
Risk Factors
• Arteriosclerosis: HTN, DM, smoking, hyperlipidaemia (including secondary to hypothyroidism)
• Glaucoma
• Ocular inflammatory disease: Behcet’s disease, PAN, sarcoidosis, SLE
• Haematological: Protein C, protein S or anti- thrombin deficiency, activated protein C resis- tance, factor V Leiden, multiple myeloma, Waldenstrom’s macroglobulinaemia, antiphospholipid syndrome
• Pharmacological: oral contraceptive pill
• Eye disease case-control study group (Risk factors for central retinal vein occlusion, The Eye Disease Case-Control Study Group 1996): HTN, DM (ischaemic CRVO), glau- coma, cardiovascular disease (ischaemic
CRVO)
Examination
• Acute CRVO: retinal haemorrhages (flame shaped and deep blot type) in all 4 quadrants of the fundus with a dilated tortuous retinal venous system, cotton wool spots, optic disc swelling, CMO
• Chronic CRVO: optociliary shunt vessels (collateral vessels connecting the choroidal and the retinal vasculature — do not leak on FFA), telangiectatic capillary bed, persistent dilatation and tortuosity, perivenous sheath- ing, NVI > NVD > NVE, CMO, glaucoma- tous optic neuropathy
• Check for an RAPD
• Check the IOP
• Look for NVI on anterior segment
examination
• Perform gonioscopy for NVA
Investigations
RCOphth RVO Guidelines 2015
• BP
• Bloods: FBC (leukaemia), ESR (myeloma),
glucose
• OCT: CMO
• FFA (if uncertain diagnosis): delayed filling of
the occluded retinal vein, capillary non-perfusion, macular ischaemia, telangiectatic vessels forming collaterals that cross the horizontal raphe
Treatment
• Control of cardiovascular risk factors: HTN, hyperlipidaemia, smoking cessation, DM
• Neovascularisation:
– Full scatter PRP: central vein occlusion
study — CVOS (The Central Vein Occlusion Study Group 1997) recom- mended that laser photocoagulation be applied only after NV is observed, with greater resolution of NVI/NVA by 1 month after PRP in 56% of no early treatment eyes (no NVI or NVA present) compared with 22% of early treatment eyes (NVI or NVA present)
• Macular oedema:
– Dexamethasone implant (Ozurdex)
NICE Guidance [TA229]: recommend as an option for the treatment of macular oedema following CRVO
GENEVA study (Haller et al. 2010): A RCT that evaluated the effects of a single dexamethasone implant compared to sham injection for the treatment of macular oedema secondary to BRVO and CRVO. Increase in BCVA of ≥15 ETDRS letters was achieved in 29% of the Ozurdex 0.7 mg group and 9% of the sham group 60 days after injection but not at 90 or 180 days.
– Ranibizumab (Lucentis)
NICE Guidance [TA283]: recommend as an option for treatment of visual impair- ment caused by macular oedema following CRVO
CRUISE study (Brown et al. 2010): A RCT to evaluate the efficacy and safety of Lucentis in the treatment of macular oedema from CRVO. Patients were ran- domised into three groups: (1) sham injec- tion; (2) 0.3 mg Lucentis; and (3) 0.5 mg Lucentis. In the first 6 months, injections were given monthly. At 6 months, both Lucentis groups gained +12.7 and +14.9 ETDRS letters (0.3 and 0.5 mg groups, respectively) compared with a gain of +0.8 letters in the control group. At 6 months, 46.2% and 47.7% of patients receiving
Lucentis 0.3 and 0.5 mg gained ≥3 ETDRS lines compared to 16.9% in the sham injec- tion group
Aflibercept (Eylea)
NICE Guidance [TA305]: recommend as an option for treatment of visual impair- ment caused by macular oedema following CRVO
CORPERNICUS study (Boyer et al. 2012): comparison of Eylea and sham injection — the proportion of patients who gained ≥15 letters from baseline in the Eylea and sham groups was 56.1% and 12.3% at week 24, respectively GALILEO study (Holz et al. 2013): com- parison of Eylea and sham injection — the proportion of patients who gained ≥15 let- ters from baseline in the Eylea and sham groups was 60.2% and 22.1% at week 24, respectively
• Delay in initiating treatment up to 6 months results in fewer visual gains compared to immediate initiation of treatment. Therefore, treatment should be initiated as soon as the diagnosis is established (RCOphth RVO Guidelines 2015)
• Careful consideration should be given to fur- ther therapy in such eyes that do not improve in terms of Snellen VA or OCT central sub- field thickness after three loading injections at monthly intervals and treatment with anti- VEGF is not recommended if no response occurs after six injections (RCOphth RVO Guidelines 2015)
• No robust data on outcomes of switching steroid to an anti-VEGF agent or switching between anti-VEGF agents or combining ste- roids with anti-VEGF agents for macular oedema due to CRVO (RCOphth RVO Guidelines 2015).
Follow Up
• Non-ischaemic CRVO (may resolve com- pletely without any complications): initial follow up every 3 months for 6 months, follow up for at least 2 years but the development of disc collaterals and the resolution of macular oedema for at least 6 months should allow the discharge of the patient from clinical supervi- sion (RCOphth RVO Guidelines 2015)
• Ischaemic CRVO: follow up after 6 months should be every 3 months for 1 year (RCOphth RVO Guidelines 2015)
• RCOphth RVO Guidelines 2015 recom- mends that oestrogen containing HRT and OCP should not be commenced in women with history of RVO. However, the continued use in a patient who develops RVO does not appear to be associated with a higher rate of recurrence.
RCOphth RVO Guidelines 2015 Treatment Algorithm
Non-ischaemic CRVO
• Baseline:
– Measurements: VA, colour fundus photog-
raphy, FFA, OCT, IOP, gonioscopy
– If VA is 6/96 or better — commence on either anti-VEGF therapy or dexametha-
sone implant (Ozurdex)
– If VA less than 6/96 — offer treatment,
high risk of NV
– If VA better than 6/12 — reasonable to
observe for spontaneous resolution
• Choice of agent: anti-VEGF preferred in eyes with previous hx of glaucoma and younger patients who are phakic, dexamethasone implant (Ozurdex) may be better choice in patients with recent cardiovascular events and in those who do not favour monthly
injections
• Re-treatment: monthly intravitreal anti-VEGF
injections are continued until maximum VA is achieved (defined as stable VA for 3 consecutive monthly assessments), once maximum VA is achieved monitor and resume treatment if VA loss occurs due to macular oedema (or treat and extend)
• Stopping treatment: consider stopping anti- VEGF therapy if after 3 consecutive monthly treatments, VA has not improved by at least five letters and CMT has not reduced from baseline/recommend stopping anti-VEGF therapy is recommended after 6 consecutive monthly treatments, VA has not improved by at least five letters and CMT has not reduced from baseline
• Switching agents: no RCT that provides evi- dence that switching to another anti-VEGF agent or intravitreal steroids may be effective. Consider switching from anti-VEGF to ste- roids or vice versa if response is poor or suboptimal.
Ischaemic CRVO
• Features suggestive of an ischaemic CRVO (RCOphth RVO Guidelines 2015)
– Poor VA
– RAPD
– Presence of multiple dark deep intraretinal haemorrhages
– Presence of multiple cotton wool spots
– Degree of venous dilation and tortuosity
– FFA showing greater than ten-disc areas
of capillary non-perfusion on seven field
FFA
– ERG: reduced b wave amplitude, reduced
b:a ratio (negative ERG) and prolonged
b-wave implicit time
• If NV occurs and AC angle is open: urgent
PRP, review 2 weeks post PRP (RCOphth
RVO Guidelines 2015)
• If NV occurs and AC angle is closed ± raised
IOP: urgent PRP with cyclodiode/GDI
(RCOphth RVO Guidelines 2015)
• Consider prophylactic PRP in ischaemic CRVO without NV if limited follow up is likely and FFA shows >30-disc areas of capil- lary non-perfusion (RCOphth RVO Guidelines
2015).
Prognosis
• At 3 years, there was a 45% chance of developing neovascular glaucoma after onset of ischaemic CRVO — highest risk if VA <6/60 or >10 DD of non-perfusion on FFA (The Central Vein Occlusion Study Group 1997)
Overall, 34% of initially perfused eyes converted to non-perfused status after 3 years (The Central Vein Occlusion Study Group 1997) Risk of CRVO in contralateral eye is 5% by 1y (RCOphth RVO Guidelines 2015).
CILIORETINAL ARTERY OCCLUSION IN A YOUNG PATIENT (CLRAO)
Causes
• Embolic: cardiac valvular disease, arrhyth- mias, cardiac septal defects, cardiac myxoma, intravenous drug use (talc)
• Coagulopathies: antiphospholipid syndrome, protein C and S deficiency, lupus anticoagu- lant, anti-thrombin III deficiency, activated protein C resistance, factor V Leiden, leukae- mia, lymphoma
• Collagen vascular diseases: SLE, PAN, Wegener’s granulomatosis
• Pharmacological: cocaine, OCP
• Infective: syphilis, toxoplasmosis, mucormycosis, lyme disease
• Retinal migraines (vasospasm): ≥2 attacks of a
fully reversible monocular positive and/or negative visual phenomena with migraine
without aura begins during the visual symptoms or follows them within 60 minutes
Examination
• Retinal whitening secondary to inner retinal oedema extending from the temporal disc into the macula in the distribution of cilioretinal artery perfusion
Investigations
• Hypercoagulability evaluation for young patients with a suggestive history (e.g. FHx, prior history, miscarriage): factor V Leiden mutation, protein C/S and anti-thrombin defi- ciencies, homocysteine levels, antiphospho- lipid antibodies
• Syphilis serology: VDRL
• Vasculitis screen: ANA, ANCA • Transthoracic/trans-oesophageal
echocardiography • ECG
• Carotid doppler US
• OCT: inner retinal oedema (acute) and inner
retinal atrophy (chronic)
• FFA: look for filling of the cilioretinal artery
during the choroidal phase
Treatment
• No proven treatments for CLRAO exist
• Refer to stroke (TIA) clinic for carotid doppler ± echocardiography if embolus identified
• Treat neovascularisation with PRP
Prognosis
• Isolated CLRAO: 90% of eyes achieve 6/12 or better vision
• CLRAO associated with CRVO: 70% of eyes achieve 6/12 or better vision
• CLRAO in conjunction with AION: 0% of eyes achieve 6/12 or better vision
USHER SYNDROME
Other Diagnoses to Consider
• RP
• CSNB
• Vitamin A deficiency
• Choroideremia
• Gyrate atrophy
• MAR
• CAR
History
• Night blindness
• Positive FHx
Examination
• Peripheral retinal atrophy with bone spicule like pigmentation
• Retinal arteriolar attenuation
• Waxy pallor of the optic disc
Investigations
• VF: constricted (ring scotoma)
• EDTs: abnormal ERG
• Audiogram: sensorineural hearing loss
Treatment
• Cochlear implantation for sensorineural deafness
• Visual impairment registration and referral to low vision aids service
• Sensory visual impairment service (specialist schools)
• Sense Usher service
• Royal National Institute of Blind people
(RNIB) website/telephone helpline
Useful facts about Ushers syndrome
• AR condition that results in RP with associated congenital hearing loss
• Occurs in 1 of every 10 deaf children (5% of all cases of congenital deafness)
• Subdivided into three groups:
– Type 1: most severe form, associated with delayed sitting and walking due to abnormal vestibular function
– Type 2: normal vestibular function
– Type 3: sensorineural hearing loss is
postlingual (as opposed to the prelingual loss in USH1 and USH2) with patients acquiring normal speech.
RHEGMATOGENOUS RETINAL DETACHMENT (RD)
Useful facts about Rhegmatogenous RD
• Incidence of RD is approximately 10 in 100,000 (Saidkasimova et al. 2009)
• Approximately 90% of patients with acute symptoms of PVD have a retinal tear at the time of initial examination. Approximately 10% of retinal tears are not seen at initial presentation or develop later (Sharma et al. 2004)
Risk Factors
• Hereditary/congenital/developmental/ degenerative
– Myopia
– Retinal breaks
– Male gender
– Hereditary vitreoretinopathies, e.g.
Sticklers syndrome
– Lattice degeneration
– Cystic retinal tuft
– Degenerative retinoschisis
• Prior ocular surgery
– Aphakia/pseudophakia
– Nd:YAG posterior capsulotomy
– Other surgery involving vitreous gel
• Prior ocular trauma
• Inflammatory
– CMV retinitis
– ARN • Other
– Fellow eye non-traumatic RD, e.g. giant retinal tear (GRT)
• Retinal Tears
• 15% of eyes with a symptomatic PVD develop retinal tears (full thickness defects in the retina) of various types
• 60% of retinal tears occur in the superotemporal quadrant
• Tears with persistent vitreoretinal traction
– Symptomatic horseshoe-shaped retinal
tears: treatment required
– Symptomatic operculated retinal tear with
vitreoretinal traction on a nearby retinal
vessel: treatment required
• Tears without persistent vitreoretinal traction
– Symptomatic operculated retinal tears without vitreoretinal traction on a nearby retinal vessel: no treatment required unless the possibility of vitreoretinal traction can-
not be excluded
• Retinal holes
– Asymptomatic atrophic retinal holes within
areas of lattice degeneration or in the outer layers of degenerative retinoschisis: no treatment required
Retinal dialysis
– Tear of the retina from its insertion at the
ora serrata
– Vitreous adherent to the posterior retina
(no tendency for posterior flap to fold over)
– Most secondary to trauma and are most commonly found in the inferotemporal
quadrant
– Treatment: observation if signs of chronic-
ity (e.g. tidemarks and retinal cysts) pres- ent, laser demarcation if limited RD, segmental scleral buckles if extensive RD
Giant retinal tear (GRT)
– A retinal tear of more than 3 clock hours of
circumferential extent
– Posterior vitreous is detached (hence poste-
rior flap has a tendency to fold over) and the
vitreous gel is adherent to the anterior flap
– Associated with high myopia, Marfan syn-
drome, Stickler syndrome, trauma
– Treatment: vitrectomy, endolaser and sili- cone oil for affected eye ± prophylactic
360° laser or cryopexy for fellow eye.
Lincoff Rules
• Describes how the location of a retinal break determines the distribution of subretinal fluid (Lincoff and Gieser 1971)
– For superotemporal or superonasal RDs,
the primary break lies within 1.5 clock
hours of the highest border of the RD
– For total or superior RDs that cross the 12 o’clock position, the primary break is at 12 o’clock or in a triangle with the apex at the ora serrata at 12 o’clock and sides extend 1.5 clock hours to either side
– For inferior RDs, the higher side of the RD indicates on which side of the optic disc the primary break is located
– For inferior bullous RDs, the primary break is located superiorly.
History
• Symptoms (flashes/floaters) and signs (Weiss ring: detachment at optic disc) of PVD
• Visual field defect for RD that has progressed sufficiently posteriorly.
Examination
• Pigmented cells (“tobacco dust”) in the vitre- ous — sign associated with a high chance of associated retinal tear
• Dilated fundus exam with 360° indentation with indirect ophthalmoscopy (for patients who present acutely with flashes and float- ers) to exclude the presence of tractional retinal tears (RCOphth Guidelines )
• Subclinical RD: SRF extending more than 1 DD from the break but not posterior to the equator
• Signs of chronicity : tidemarks (present from 3 months: imply stability of the extent of the detachment), intraretinal cysts (present from 1 year), PVR.
Investigations
• B-scan: if poor fundal view present
Treatment
• Round hole RD
–
Laser demarcation:
For asymptomatic RD’s or those with minimal symptoms
–
• Detachment due to retinal dialysis
Segmental scleral buckling
– Laser demarcation
– Segmental scleral buckling
• Detachment secondary to U (horseshoe) tears
– Laser demarcation:
Small asymptomatic peripheral detachment
Although laser photocoagulation cre- ates an instant adhesion this is not up to full strength for up to 14 days — rap- idly progressing fluid may extend through the area of demarcation before a strong enough adhesion develops
– Pneumatic retinopexy
Detachments with breaks limited to one quadrant, usually superior
– Scleral buckling Young patients
Anteriorly located small holes with
localised RD in phakic patients
– Vitrectomy
Older patients with a liquefied vitreous Wide and bullous RD
Presence of breaks in multiple quadrants Presence of RD with marked traction with different anterior posterior depth of breaks Absence of an apparent retinal break in a pseudophakic patient
GRT RD
Macular hole RD
Prophylactic therapy for asymptomatic retinal tears in phakic non-fellow eyes is usually not recommended except for an inferior retinal dialysis and for a non-traumatic GRT that occurred in the first eye
Maximum strength of chorioretinal adhesion following laser photocoagulation is achieved between 3 and 14 days later (stronger adhe- sion than normal appears within 24 h of the application of treatment).
The RCOphth Ophthalmic Services Guidance
for the Management of Acute Retinal Detachment 2010
• Retinal tears
– Tractional (horseshoe) retinal tears should
be treated urgently with laser photocoagulation or cryotherapy
– Asymptomatic retinal breaks and atrophic
round holes do not require any treatment
– Asymptomatic retinal breaks and atrophic round holes with localised subretinal fluid may require treatment (localised RD is often asymptomatic, progresses very gradu- ally if at all) but does not need to be treated as an emergency — non urgent referral is recommended to a local retinal specialist or department to determine what management
is best tailored to the patient needs
• Reduce progression of RD
– Bed rest
– Dependent posturing: posture with tear at
the lowest location
• RD surgery
– Urgent surgery required if RD is reaching within 1 DD of the fovea, particularly with a superior bullous detachment
– Where there is imminent danger of foveal detachment and expertise and facilities to operate urgently are unavailable locally, a transfer should be agreed to a suitably equipped and staffed unit with an available VR surgeon.
MACULAR HOLE ( MH)
Differential Diagnosis
• Lamellar hole
– Absence of a contractile ERM
– Defects in the inner fovea with cleft
between the inner and outer retina
– Bi- or tri-lobulated red central circular
defect on biomicroscopy
– Negative Watzke-Allen test (thin beam of
light projected over hole — broken or
thinned centrally in MH) • Pseudohole
– Presence of a contracted ERM with thick- ening of the macula
– U or V shape of the fovea
Key facts about macular holes
• Round opening in the foveal center
• Occurs in middle-aged or elderly patients
• More common in females
• Incidence is approximately 7.8 per 100,000 population (McCannel et al. 2009)
• Prevalence of 1/3300 (McDonnell et al. 1982)
Risk Factors
• Age ≥65 years old
• Female sex
Causes
• Idiopathic: due to abnormal vitreofoveal traction
• Secondary
– Trauma: sudden axial compression of the eye resulting in equatorial expansion and retinal rupture of the fovea
– Pathological myopia
– VMT/ERM
– Chronic CMO.
Classification
• Biomicroscopy (Gass Classification)
– Stage 1a (impending MH): focal central
yellow spot, loss of foveal depression
– Stage 1b (occult MH): yellow foveolar ring
– Stage 2 (full thickness MH): central round
<400 μm diameter retinal defect
– Stage 3 (full thickness MH): central round ≥400 μm diameter retinal defect, no Weiss ring
– Stage 4 (full thickness MH): stage 3 with
Weiss ring (PVD)
• OCT
– Stage 1a: inner foveal cyst
– Stage 1b: inner foveal cyst completed by
disruption of the outer retina up to the RPE, posterior hyaloid still attached to the intact roof of the cyst
– Stage 2: disruption in roof of the cyst with a partially detached operculum from hole edge
– Stage 3: complete absence of the roof with vitreous completely detached form the retinal surface over the posterior pole and is
not connected to the hole edge
– Stage 4: OCT unable to diagnose stage 4
MH, stage 4 MH remains a diagnosis from biomicroscopy with the presence of a Weiss ring
The International Vitreomacular Traction Study Classification System (Duker et al. 2013)
– Vitreomacular adhesion (VMA): vitreous
adhesion to central macula with no demon-
strable retinal morphologic changes
– Vitreomacular traction (VMT): vitreous adhesion to central macula with demon- strable changes by OCT but no full thick- ness tissue dehiscence; may include the following: cystoid changes in macula, ele- vation of fovea above RPE, tissue cavita-
tion, loss of foveal contour
– Small full thickness MH: hole ≤250 μm,
may be round or have a flap adherent to vit- reous; operculum may or may not be present
Medium full thickness MH: hole >250 μm but ≤400 μm; may be round or have a flap adherent to vitreous; operculum may or may not be present
Large full thickness MH: hole >400 μm; vitreous more likely to be fully separated from macula
Impending MH: term used when a full thickness MH is observed in one eye and VMA or VMT is observed on OCT in the fellow eye
Lamellar MH: partial thickness foveal defect that typically appears on biomicro- scopically as a round or oval, well- circumscribed, reddish lesion. Anatomic OCT-based features of lamellar MH include the following: (1) a defect in the inner fovea (may not have actual loss of tis- sue); (2) maintenance of an intact photore- ceptor layer (lamellar MH can be distinguished from full thickness MH on OCT by the presence of intact photorecep- tors at the base); (3) an irregular foveal contour; (4) intraretinal splitting (schisis), typically between the outer plexiform and outer nuclear layers
Macular pseudohole: Anatomic OCT-based features of macular pseudohole include the following: (1) invaginated or heaped foveal edges; (2) steep macular contour to the central fovea with near-normal central foveal thickness; (3) concomitant ERM with central opening; (4) no loss of retinal tissue
Examination
• Yellow spot (stage 1a)
• Yellow foveal ring (stage 1b)
• Central red round area at the fovea (stage 2–4)
• Positive Watzke-Allen test: shine a vertical
thin beam of light using the slitlamp over the macular hole — narrowing or gap in the beam of light is seen in macular holes (Tanner and and Williamson 2000).
Investigations
• OCT:measurementsinMHincludebasediam- eter (BD — linear dimension of MH at the level of the RPE layer) and minimum linear diameter (MLD — minimum horizontal diameter in the scan in an area excluding the operculum)
Treatment
Idiopathic MH – Observation:
For stage 1 MH: high rate of spontane- ous resolution. Surgery has shown no benefit (Smiddy et al. 1988; de Bustros 1994)
– Medical
NICE Guidance [TA297] — Ocriplasmin is an option for treating VMT in adults only if:
• An ERM is not present and
• They have a stage 2 FTMH with a
diameter of ≤400 μm and/or • They have severe symptoms
– Surgical
Vitrectomy + ILM peeling + gas tam- ponade for holes without VMA
Traumatic MH
– High spontaneous closure rate (50%).
Recommended to wait 4 months from the trauma before surgical intervention (Yamashita et al. 2002).
Prognostic Factors for Treatment of Idiopathic MH
• Preoperative VA: eyes with better preoperative VA achieve higher rates of anatomical closure and visual gain
• Preoperative BD and MLD measurement: smaller preoperative MLD and BD measure- ments are associated with better visual out- comes and anatomical closure
• Duration of symptoms: anatomical closure and visual outcomes were higher in patients with a shorter duration of symptoms.
Face Down Posturing for Idiopathic MH
• Cochrane review (Solebo et al. 2011) of three RCT’s that directly compared face-down pos- turing following idiopathic MH surgery with no face-down posturing:
– For MH ≤400 μm, face down posturing had no significant effect on successful hole closure
– Two of the RCT’s found that there was a significant benefit of face-down posturing for successful closure when the diameter was >400 μm
– Face down posturing for at least 5 days postoperatively should be recommended for patients with MH >400 μm in size and holes >1 year in duration.
Development of Idiopathic MH in Fellow Eyes
• A fellow eye with PVD has a <1% risk of pro- gressing to a MH (Ezra 2001)
• A fellow eye without a PVD has a 15.6% risk of progressing to a MH over 5 years (Ezra et al. 1998).
Success Rates for Idiopathic MH Closure
• 88% success rate for stage 2 macular holes (Ruby et al. 1994)
• 69% success rate for stage 3 and 4 macular holes (Freeman et al. 1997)
• Holes <400 μm have a 94% chance of closure compared with 56% for those 400 μm or more (Ip et al. 2002).
Post-OperativeComplications of Surgery
• Retinal tears during surgery: 12.7% with PVD induction and 3.1% without PVD induction (Chung et al. 2009)
• Retinal detachment: 6.6–14% (Guillaubey et al. 2007)
• Re-opening of the hole: 11% (Bhatnagar et al. 2007) especially in those who have postoperative cataract extraction
• Cataract
• Endophthalmitis
TOXOPLASMOSIS
Other Diagnoses to Consider
• Infectious: TB, syphilis, rubella, CMV retinitis, herpes simplex, toxocariasis
• Non-infectious: sarcoidosis
History
• Symptoms: asymptomatic, floaters, reduced vision
• Immunocompromised: post organ transplantation, HIV positive, therapeutic immunosuppres- sion for systemic disease (e.g. SLE, RA, GPA).
Examination
• Acute lesions: intensely white focal lesions with overlying vitreous inflammatory haze adjacent (“headlight in the fog”) to old hyper-pigmented scars (satellite lesions),
periphlebitis
• Chronic lesions: hyperpigmented scars with an atrophic centre devoid of all retinal and choroidal elements — the underlying sclera gives the lesion its white centre
• Check the IOP
• Perform an anterior segment examination to
look for any visually significant cataract.
Investigations
• VDRL: rule out syphilis
• ACE, CXR: rule out sarcoidosis
• HIV serology: rule out HIV
• Pregnancy test
• Anti-toxoplasma IgM and IgG antibodies:
– Negative IgG and negative IgM antibodies implies infection has not occurred
– Positive IgG and negative IgM antibodies implies an infection that was in the distant past
– Positive IgM antibodies may suggest a recently acquired infection.
3.10.5 Treatment
• Inflammation
– In immunocompetent patients, the disease
is self-limiting and does not require treat-
ment unless sight threatening
– Indications for treatment:
Lesions involving the disc, macula, or papillomacular bundle
Lesions threatening a major vessel Marked vitritis
Any lesion in an immunocompromised
patient
– No corticosteroids if patient is
immuno-compromised
– Triple therapy: pyrimethamine, sulfadia-
zine, folinic acid, corticosteroids
– Co-trimoxazole (trimethoprim +
sulfamethoxazole) + corticosteroids
– Intravitreal dexamethasone + clindamycin
– Oral clindamycin
– Spiramycin or atovaquone if maternal infection acquired during pregnancy (15% in the first trimester and 60% in the third trimester risk of fetal transmission if acquired during pregnancy)
• Cataract extraction once uveitis is inactive for ≥3 months.
VOGT KOYANAGI HARADA SYNDROME ( VKH)
Other Diagnoses to Consider
• Sympathetic ophthalmia: history of penetrating eye injury
• Sarcoidosis
• Posterior scleritis: T-sign on B-scan
• Uveal effusion syndrome: lacks intraocular inflammation
• Acute posterior multifocal placoid pigment epitheliopathy (APMPPE)
Key facts about VKH syndrome
• VKH syndrome is a bilateral granulomatous inflammatory panuveitis often associated with exudative RD and with extraocular manifestations
• No history of penetrating ocular trauma or surgery preceding initial onset of uveitis
Examination
• Systemic features
– Cutaneous not preceding ocular/CNS
disease: Vitiligo
Poliosis
Alopecia
– Neurological
Sterile meningism: headaches, neck stiffness, photophobia
Encephalitis
CN palsies
– Auditory Tinnitus
Deafness
Vertigo
• Ocular features
– Prodromal stage:
Non-specific viral like illness Meningism
– Acute uveitic stage:
Bilateral panuveitis: anterior uveitis, multifocal choroiditis
Multiple serous RD’s
Optic disc swelling
– Chronic uveitic stage (convalescent phase): Vitiligo
Perilimbal vitiligo — Sugiura’s sign Poliosis
Choroidal depigmentation: pale optic disc with bright red-orange choroid (sunset glow fundus)
Small yellow well circumscribed areas
of chorioretinal atrophy
– Chronic recurrent stage:
Acute episodic exacerbations of granu- lomatous anterior uveitis
Subretinal choroidal neovascular membrane
Cataracts (posterior subcapsular)/ glaucoma
Investigations
• B-scan: choroidal thickening
• OCT: serous RD
• FFA: multifocal areas of pinpoint leakage, focal areas of delay in choroidal perfusion, large placoid areas of hyperfluorescence
• LP: CSF pleocytosis
Treatment
• Inflammation: high dose systemic corticoste- roids ± immunosuppresants
• CNV membrane: anti-VEGF agents (avastin) • Cataracts: cataract extraction if VA reduced and uveitis absent for a minimum of 3 months
• Glaucoma: drops, surgery
MALATTIA LEVENTINESE/ DOYNE HONEYCOMB RETINAL DYSTROPHY
Other Diagnoses to Consider
• AMD
• Fundus flavimaculatus: flecks do not hyperfluoresce on FFA, subnormal EOG, ERG and dark adaptation normal
• Sorsby macular dystrophy
• Pattern dystrophies
• Best disease (in its later stages)
Examination
• Presence of multiple elongated yellow-white deposits between the RPE and inner collagenous zone of Bruch’s membrane in a radiating pattern throughout the macula that is present early in life (often by the second decade).
• These elongated drusen may also be found outside the arcades, especially nasal to the disc, which is unusual in other types of macular degeneration.
• These drusen may also be found in some patients in a peripapillary pattern or on the margin of the disc itself.
• Coalescence of drusen may simulate a vitelli- form lesion
• RPE atrophic changes ± chorioretinal atrophy
Investigations
• OCT: hyperreflective thickening of the RPE- Bruch membrane complex, associated with localised dome-shaped elevations
• FFA: during the arterial phase, multiple, round, sharply defined fluorescent spots corresponding to the lesions observed at ophthalmoscopy, no leakage of fluorescein is seen
• EDTs: ERG, EOG, dark adaptation normal in the initial stages
• Genetic testing: single mutation in the fibulin-3 gene
Treatment
• Genetic counselling and discussion with patient
• CNV: anti-VEGF agents
APPROACH TO ADULT WATERING EYE
History
• “Do the tears flow down your cheek or do they stay in your eye?”: watery eye (no spilling of tears onto the cheek) vs tearing eye (tears overflow onto the cheek)
• “Do the tears flow down your cheek inside when you are resting or mainly when you are outside in cold or wind?”: partial obstruction (if tearing only present in the wind and cold) vs complete obstruction
• “Is the problem unilateral or bilateral?”: tearing eye (i.e. obstruction in lacrimal drainage system) usually unilateral, watery eye usually bilateral
• Ask about findings suggestive of obstruction of the lacrimal system: unilateral symptoms, epiphora, history of dacryocystitis, onset after conjunctivitis (obstruction of puncta or cana- liculi), facial fracture (damage to NLD), or nasal surgery (history of nasal surgery — damage to NLD)
• Ask about any prosecretory drugs, e.g. oral pilocarpine for Sjogren Syndrome
Differential Diagnosis of a Watery Eye in an Adult
• Poor tear film: blepharitis/MGD
• Reflex tearing: entropion, trichiasis, reduced
or incomplete blinking from parkinsonism, incomplete eyelid closure from CN VII palsy
• Inadequate lacrimal pump: ectropion, CN VII palsy (reduced strength of eyelid closure), lid laxity
Differential Diagnosis of a Tearing Eye in an Adult
• Result of canalicular or NLD obstruction
– Children: congenital NLDO
– Young adults: trauma (canalicular lacera-
tion or facial trauma), canalicular obstruc- tion (post viral conjunctivitis with scarring of each canaliculus)
– Middle-aged adult: dacryolith (episodes of recurrent epiphora which resolves sponta- neously ± signs of acute dacryoadenitis)
– Older adults: primary NLDO (PANDO): scarring in distal portion of NLD, symp- toms include: epiphora, chronic mucopuru- lent discharge (chronic dacryocystitis) and acute cellulitis of the lacrimal sac (acute dacryocystitis)
3.13.4 Examination
• Examine for possible causes of a watery eye – Eyelid problems:
Ectropion and entropion
Lacrimal pump problems — CN VII palsy, lid laxity — lid distraction test (manually pulling lower eyelid away from eyeball: more than 6 mm off eyeball implies lid laxity) and snap test (measure horizontal lid laxity by pulling the lower eyelid inferiorly toward the inferior orbital rim. Eyelid with no laxity will spring back into position with- out a blink. Can be quantified by counting no. of blinks before eyelid returns to normal position)
Punctal problems — eversion of punc- tum, canaliculitis (swelling and erythema of the canalicular portion of the eyelid, pouting punctum with dilated punctum, pressure on canaliculus expresses pus), congenital punctal atresia (one or more punta are absent), stenosis of punctum (antiglaucoma drops, phospholine iodide, following eyelid eversion such as with an ectropion — stenosis resolves once lid position restored)
– Eyelash problems — trichiasis secondary to marginal entropion, blepharitis/MGD (keratin plugging, posterior lid telangiecta- sia, hyperaemia of eyelid margin)
– Tear film abnormalities — meniscus high/ low, faster TBUT (<10 s), Schirmer’s test
• Examine for possible causes of a tearing eye – Lacrimal examination:
Rule out dacryocystitis first: diagnosis of NLDO is made if signs of acute dac- ryocystitis (erythema, swelling, and ten- derness in the medial canthus) are present, you can express pus/mucoid from lacrimal sac, or a mucocele is pres- ent (palpable cystic mass present in medial canthus caused by obstruction at both the NLD below and common inter- nal punctum above causing lacrimal sac to fill with mucus)
Evaluate tear lake with slit lamp: enlarged if obstruction pres- ent — mucoid/pus in tear lake if NLD obstructed, no debris in tear lake if punctum or canaliculi obstructed Evaluate cornea — rule out any pathologic changes, watch patient blink spontaneously to see how much cornea is covered with a blink
Evaluate lid margins for signs of bleph- aritis or marginal entropion
Evaluate position of punctum — normal punctum not easily visible without slight manual eversion of the eyelid Check lacrimal system vital signs:
• Dye disappearance test: 2% fluores- cein into each fornix. After 5 min, check to see how much dye is retained in eye. Normal result docu- mented as spontaneous symmetric dye disappearance. An abnormal result is recorded as dye retained in right or left eye,
• Lacrimal probing to demonstrate patency of upper and lower canaliculi using a lacrimal probe: probe should be placed vertically in the punctum for 1–2 mm. Lid pulled temporally and probe directed towards the can thal angle. Probe should pass easily to lacrimal sac where a hard stop (lacrimal bone) is felt. A soft stop indi- cates canalicular obstruction. Lacrimal irrigation: using a lacrimal irrigation cannula in the lower cana- liculus, not the sac, you should be able to irrigate saline easily into the nose without any reflux around the cannula or out the upper canaliculus (normal NLD). If you cannot irrigate with pressure on syringe then the duct is closed (anatomic obstruc- tion — regurgitation through same canaliculus irrigated through if obstruction in upper or lower cana- liculus, regurgitation through oppo- site canaliculus than the one irrigating through if common canaliculus obstruction). If you can irri- gate with pressure on syringe then duct is partially obstructed (functional obstruction)
Perform a nasal examination — nasal endoscopy if possible, to rule out intranasal tumours or mucosal abnormalities
Investigations
• Dacryoscintigraphy (DSG): indicated for functional NLDO (patient gives hx typical of PANDO but you cannot demonstrate an obstruction) and gives an estimate of the phys- iologic drainage of tears. If any delay is noted (delayed filling of NLD), a DCR is recom- mended (DCR not recommended if no filling of NLD seen)
• Dacryocystogram (DCG): useful if previous trauma, destructive disease (inflammatory) or suspected tumour
• Jones testing — considered in cases of partial obstruction to determine level of block:
– Jones I — physiological without syring-
ing — 2% fluorescein into lower fornix, after 5 min, assess dye recovery with a cot- ton bud placed at NLD opening at inferior meatus, positive if dye recovered and implies normal patency, negative if no dye recovered and implies partial obstruction
or lacrimal pump failure
– Jones II — non-physiological after syring-
ing — wash out fluorescein from fornix, insert lacrimal cannula into the lower canaliculus and irrigate, assess dye recovery from nose as before, positive if dye recov- ered and implies partial obstruction of NLD, negative if no dye recovered and implies partial obstruction above the lacri- mal sac (punctal or canalicular obstruction)
Treatment
• In all cases, eyelid and eyelash problems should be treated before lacrimal surgery
• Poor tear film: lid hygiene, lubricants, punctal plugs, punctal cautery
• Reflex tearing: treat entropion, lubricants
• Lacrimal pump problems: ectropion/laxity of lower eyelid — LTS, CN VII palsy — lubricants, LTS, gold weight placement in upper
eyelid
• Punctal stenosis: discontinue treatment with
any known offending eye drop, two- (vertical cut of punctum and horizontal cut of canalicu- lus) or three-snip (excision of a small triangle of the posterior wall of the vertical and hori- zontal portion of the canaliculus) punctoplasty
• Punctal eversion: if no lid laxity pres- ent — medial spindle procedure (combination of a posterior lamella shortening procedure and a mechanical inversion of the lid margin) only, if lid laxity present — LTS ± medial spindle procedure (LTS alone may return punctum to normal position — check at slit- lamp to assess for this)
• Canaliculitis: curette the canaliculus through a dilated punctum ± punctoplasty (keep curet- ting until you do not retrieve any more sulfur granules or “stones”) — topical antibiotic drops post-operatively
• Canalicular obstruction: canalicular recon- struction over stents (lacerations or localised obstructions following trauma), DCR with Lester-Jones tube placement (Pyrex tube that carries the tears from the conjunctival cul-de- sac through a DCR ostium into the nose, bypassing the obstructed canaliculi — see
Table 3.5)
• Acute dacryocystitis: do not probe or irri-
gate, oral or IV antibiotics, if lacrimal sac abscess (see Fig. 3.17) is present — incision and drainage of the lacrimal sac through an external incision will speed recovery but risks formation of a fistula, DCR (external/ endonasal) delayed until inflammation has settled
• Chronic dacryocystitis (mucopurulent dis- charge but with no signs of cellulitis): topical antibiotics and DCR (external/endonasal), do not probe or irrigate
• Suspected dacryolith: if more than two epi- sodes occur within a year, a DCR (external/ endonasal) is a reasonable therapeutic option.
• Functional NLDO (anatomically the NLD is open on irrigation but the tears do not seem to pass into the nose spontaneously under nor- mal conditions): DCR or silicone stent intuba- tion of the NLD (remove stents at 6 months post op — success about 75%)
Key facts about a Lester-Jones tube
Anatomy
• The proximal end of the tube lies at the medial commissure and the distal end lies within the middle meatus of the nose
Indications
• Symptomatic epiphora secondary to extensive scarring of both upper and lower canaliculi
• Congenital atresia or complete absence of the canaliculi with epiphora
• Symptomatic epiphora secondary to lacrimal pump failure, e.g. chronic facial palsy
• Failed re-do DCR
• Chronic epiphora due to eyelid malpositions which eyelid surgery has failed to or is unable to control, e.g. ichthyosis, severe chronic eczema
Complications
• Tube displacement — scleritis from local scleral indentation and irritation • Tube obstruction
• Lacrimal sac infection
APPROACH TO PAEDIATRIC WATERING EYE
History
• Onset: soon after birth or if it is more recent
• Photophobia: suggests congenital glaucoma, uveitis, corneal disease (e.g. cystinosis), FB in
conjunctival sac
• Eye rubbing or poking: suggests a retinal dys-
trophy such as LCA
• Watery nose on same side as the watery eye:
suggests excessive lacrimation rather than blocked tear drainage
Examination
• External examination
– Tearing, red macerated skin, stickiness
may be seen
– In NLDO, tear lake is thickened, brimming
the lower lid margin — measures 2 mm or more with fluorescein staining of the tear film (normally <1 mm)
– Secondary bacterial conjunctivitis with generalised conjunctival redness
– Perilimbal conjunctival injection more spe- cific for keratitis or uveitis
– Generalised corneal haze with secondary corneal epithelial oedema may be a sign of glaucoma — estimate horizontal corneal diameter using a ruler held close to the lid
– Congenital swelling over the nasolacrimal sac is probably a dacryocystocele
• Slit lamp examination
– Puncti: presence or absence, ectropion
– Lid: epiblepharon with inturned eyelashes,
blepharitis
– Conjunctiva: inspect inferior conjunctival
fornix looking for diffuse redness and swelling of the conjunctiva — suggesting chlamydia conjunctivitis
– Cornea: crystals, abrasions, FB, ulcers, KP’s, Haab striae and corneal oedema
– AC: hypopyon,
– Iris: posterior synechiae
– Lens: cataract
• Fluorescein testing
– Staining with abrasions or epithelial
oedema
– Dye disappearance test
• IOP
• Fundus examination
– Disc cupping in glaucoma
– Posterior segment pathology, e.g. retino-
blastoma (can present as a red watery eye
with a pseudo-hypopyon)
• Cycloplegic refraction, fundus examination
– Unilateral myopia in a child with unilateral glaucoma
Differential Diagnosis
•
Reflex tearing (lacrimation)
– Lids:
Blepharitis
Epiblepharon (see Fig. 3.18): irritation from inturned eyelashes
– Conjunctiva:
Conjunctivitis: infective (viral, bacterial), allergic, chemical
Conjunctival sac or subtarsal FB
– Cornea: Corneal FB
Corneal abrasion Keratitis Cystinosis
– Congenital glaucoma (see Sect. 9.4): horizontal corneal enlargement, Haab striae, buphthalmos, increased CDR, raised IOP
– Anterior uveitis Decreased lacrimal drainage
– NLDO
– Lid malposition
– Punctal malposition
– Punctal occlusion (punctal atresia)
– Anomalous drainage system (blocked or
absent) with craniofacial abnormalities
CONGENITAL NASO LACRIMAL DUCT ONSTRUCTION (CLNDO)
Key facts about CLNDO
Caused by a persistent membranous obstruction at the valve of Hasner — in more than 90% of patients, this membrane will spontaneously rupture within the first year of life
• Diagnosis is made on a history of a watery eye that has been present from the first few weeks of
birth — usually unilateral but may be asymmetrically bilateral
Examination
• Child is well with no evidence of irritation or photophobia
• Periocular skin may become red and excoriated
• Stickiness or crusting of the lashes
• Eye remains white without evidence of active infection, although conjunctivitis may compli-
cate the condition
• Increased tear meniscus
• Mucocele may develop — contents can be
expressed into the conjunctival sac
Investigations
• Dye disappearance test:
– Fluorescein 1% is instilled into each lower
conjunctival fornix and cobalt blue light
from the slitlamp illuminates the eyes
– Tear meniscus evaluated at 5 min
– –
Normally fluorescein disappears from tear meniscus by 5 min but remains present in children with obstruction
Grading (MacEwan and Young 1991):
0 = no fluorescein
1 = thin fluorescing marginal tear strip
2 = more fluorescein persists, higher tear film 3 = wide, brightly fluorescing tear strip, spillage
Treatment
• Conservative (for the first year of life as high rate of spontaneous resolution):
– Crigler massage: must push index finger
posterior to the anterior lacrimal crest to empty the sac, idea is to massage as often as necessary to empty the sac — massage may build up enough pressure in the sac so that the membrane is broken
– Antibiotics if conjunctivitis present (avoid antibiotics in watery white eyes)
• Syringing and probing (performed when spontaneous resolution of the tearing and mat- tering does not occur by 1 year of age) — 90% success rate:
– Procedure performed under GA in an out- patient setting
– Patient preparation — spray a vasocon- stricting agent in the nose
– Dilation of the punctum using a Nettleship dilator
– Passage of probe into the sac until a “hard” stop is felt
– Rotation of the probe 90° and passage of the probe into the NLD about 15 mm aim- ing slightly posteriorly and laterally
– Fluorescein-stained saline irrigation using a disposable cannula
– Confirmation that probe is in the nose (suc- tion fluorescein tinged saline irrigation fluid — suction is in nose whilst canaliculus is irrigated with fluorescein stained saline)
– Apply topical antibiotic ointment
• NLD intubation with silicone stents (per-
formed when probing fails):
– The upper and lower canalicular stents are
tied so that the knot lies underneath the inferior turbinate
– Leave stents in place for 6 months
– A small amount of tearing will often remain with the stents in place, especially when child has a cold (no discharge should be
seen however)
– Remind parents that tears do not flow
through the stents and that any residual tearing usually resolves when the stents are removed
– If prolapse of stents occur — stents cannot be repositioned because the knot is up in the duct so just tape the loop to the cheek
DCR (indicated with persistent epiphora despite probing and intubation).
APPROACH TO A PATIENT WITH PROPTOSIS
History
• Pain: caused by inflammation, infection, acute pressure changes (haemorrhage), and a highly malignant tumour growing into bone or nerves (neoplasms in general do not cause pain until a complication related to the neoplasm arises)
• Progression: rapid (hours to days — suggest inflammation or infection), intermediate (weeks to months — suggests more chronic types of inflammatory processes such as thy- roid disease), slow (months to years — sug- gests a benign neoplasm or lymphoma)
• Past medical history: any previous neoplasm elsewhere such as lymphoma or breast carci- noma, any past trauma of the face (caused facial asymmetry that may accentuate or diminish the appearance of a proptotic eye), any history of thyroid disease
Examination
• Orbital examination: start by evaluating the change in the position of the eye in terms of axial and non-axial displacement, next palpate the orbital rims and soft tissues to see if any abnormality is present, then you will check briefly for any pulsations, last you will search for other clues in the periocular area that may give you information to develop a differential diagnosis
• Proptosis: axial displacement in anterior direction (thyroid orbitopathy with enlarge- ment of the EOM, optic nerve tumours or a benign cavernous haemangioma). Measure axial displacement with Hertel exophthalmometer.
– Inferior displacement (problems arising in the area of the lacrimal gland, defects in the orbital roof due to trauma, encepha- locele, or frontal sinus mucocele formation)
– Lateral displacement (problem in the eth- moid sinus — subperiosteal abscess — an acute process — arising in the ethmoid sinus and extending into the subperiosteal space, sinus carcinomas — slowly progres- sive process, mucocele — very slowly pro- gressive process)
– Upward displacement (lymphoid lesion, maxillary sinus tumours)
– Medial displacement (enlarged lacrimal gland).
Measure non-axial displacement with a
Ruler or McCoy Tri-Square
• Palpation: start with palpation of the orbital rims and then move toward the eye, palpating the superior and inferior fornix for any ante- rior masses — if present determine size, shape and position, determine if there is any tender- ness in the area of the lesion (infectious or inflammatory disorders will often cause the
skin to be erythematous and warm to touch)
• Pulsation: pulsations of the eye suggests either an arterial vascular malformation in the orbit (if high flow you may be able to hear a bruit or feel a thrill) or the absence of orbital bone that allows the normal pulsations of the brain to push on the eye (e.g. absence of sphenoid wing in NF-1), venous lesions do not pulsate but they will usually show enlargement with the Valsalva manoeuvre (orbital or conjuncti- val varix) or with the head in a dependent
position
• Periocular changes: temporal flare of the lateral position of the upper lid and lid lag seen
on downgaze (thyroid orbitopathy), conjuncti- val salmon patch (orbital lymphoma), fullness of the temple (sphenoid wing meningioma), periocular skin malignancy (intraorbital spread of cutaneous carcinoma)
Investigations
• Orbital imaging serves two purposes — providing diagnostic information (what the mass is) and providing information used to plan orbitotomy (want to know the best surgical approach to biopsy the mass)
• CT for bony orbital trauma
• MRI for imaging of the orbital apex, chiasm,
optic nerve tumours, FLAIR sequence for optic neuritis due to demyelinating disease, STIR sequence for thyroid orbitopathy
ORBITAL DISEASE OCCURING IN ADULTS
Differential Diagnosis
• Axial displacement:
– Enlarged EOMs — thyroid orbitopathy,
orbital pseudotumour
– Intraconal mass — cavernous haemangioma
– Optic nerve tumour — optic nerve
meningioma
• Nonaxial displacement:
– Inferior displacement — lacrimal gland (benign mixed or lymphoid tumour), fron- tal sinus (mucocele), orbital roof (sphenoid wing meningioma)
– Lateral displacement — ethmoid sinus (abscess or mucocele)
– Superior displacement — maxillary sinus (carcinoma), orbital fat (lymphoid tumour)
– Medial displacement (rare) — benign mixed tumour of lacrimal gland
• Enophthalmos:
– Scirrhous carcinoma of the breast — infiltrative sclerosing tumour
THYROID EYE DISEASE
Key facts about TED
• Most common cause of unilateral or bilateral proptosis
• Affects women five to six times more often than men
• Onset most common in the early 40s and mid-60s
• TED is most commonly associated with Graves
disease (90%) but may occur in 3% of Hashimoto’s thyroiditis, 6% euthyroid, and 1% primary hypothyroidism
• Allergic conjunctivitis — acute in onset from a new exposure, causes itching, papillary con- junctival reaction, not associated with eyelid retraction or proptosis
• Myasthenia gravis — diplopia worsens throughout the day and improves after rest (not variable in TED), may present with ptosis (not associated with TED)
• Orbital myositis — causes enlargement and inflammation of the muscle body and tendon insertion (muscle body only in TED), not associated with eyelid retraction, usually uni- lateral (bilateral presentation unlikely for orbital myositis, TED can present unilaterally or bilaterally)
• Orbital tumours — typically unilateral in pre- sentation causing proptosis and ocular motil- ity disturbances, unlikely to cause eyelid retraction or lid lag
• Carotid-cavernous fistula — patient may hear pulse-synchronous tinnitus, presentation may include pulsatile proptosis, dilated conjunctival and episcleral vessels, elevated IOP, enlarged EOM, would not cause eyelid retraction or temporal flare
• CPEO — slowly progresses over 5–15 years with most patients presenting with ptosis, all cardinal directions of gaze are affected, with downgaze most likely spared (TED conversely typically affects downgaze and nasal gaze)
• Inflammatory orbitopathy (e.g. GPA) — GPA typically presents with a mix of upper and lower respiratory tract and renal pathologies. Patients may have conjunctivitis, episcleritis, scleritis, and/or uveitis (other than conjuncti- vitis, these findings are uncommon in TED patients)
• IgG4-related orbitopathy — painless swelling of the EOM’s, lacrimal glands, and infraor- bital nerves in combination with paranasal sinus disease, multi-organ fibrosis and sclero- sis (pancreas, liver, salivary glands, retroperitoneum) may co-exist
History
• Any pain and rate of progression: gradual onset, slow progression without pain. No pain is associated, but discomfort, more like pres- sure or orbital fullness, is often present
• Any diplopia (restrictive strabismus) or blurred vision (optic nerve compromise)
• Ask about symptoms of hyper- or hypo-thyroidism
• Past medical history often reveals systemic thyroid disease
• A family history is common
• Ask about risk factors for TED: smoking, his-
tory of thyroid disease (hyper- or hypo-thy- roidism), poor control of thyroid function is a risk factor for reactivating TED
Examination
• Check lids
– Measure the eyelid position and function
(PA, MRD1, LF)
– Look for lid swelling and erythema
– Look for upper and lower lid retraction
– Look for temporal flare of the upper eye-
lid — lid just keeps getting higher toward the lateral canthus (peak of normal eyelid is just nasal to the pupil)
Look for lid lag in downgaze.
–
• Check proptosis
Look for lagophthalmos
– Measure the degree of proptosis using an exophthalmometer
– Axial, usually bilateral, but can be quite asymmetric
• Check optic nerve function for compressive optic neuropathy
– VA
– RAPD
– Colour vision: first sign of early optic nerve compression is reduced colour vision
– 24-2 HVF
–Serial visual evoked potentials
(VEP — provides objective assessment of optic nerve function — important to know that patient is euthyroid before evaluating the result, as hypothyroid patients without optic nerve compression can show a delay in the P100 component of the VEP)
• Slit lamp examination
– Check corneal sensation
– Look for conjunctival and caruncular injec-
tion and/or chemosis
– Look for signs of corneal exposure, supe-
rior limbic keratoconjunctivitis
– Check IOP in primary position and upgaze
(more than 5 mmHg difference)
– Perform a dilated fundus exam to look for optic disc swelling or pallor and choroidal
folds
• Check extraocular muscle involvement
– Mechanical restriction of ocular movement ± pain on looking in the direction of lim- ited movement
– Retraction of the globe occurs when move- ment away from the site of the restriction is attempted (commonly seen on upgaze)
– In order of decreasing frequency, the mus- cles involved are: IR muscle (restricted up gaze), MR muscle (restricted abduction), SR muscle (restricted downgaze), LR mus- cle (restricted adduction although LR is usually spared even when enlargement is evident on CT scan)
– Common ocular posture is hypotropia of the more affected eye, sometimes with associated ET
– An abnormal head posture, commonly chin elevation, is often adopted, ± face turn: purpose is to avoid an uncomfortable posi- tion of gaze, to centralise a field of binocu- lar single vision
– Enlarged vertical fusion amplitude
• Systemic examination
– Examine for goitre, palmar erythema, atrial fibrillation, and pretibial myxedema
– Look for signs of hyperthyroidism (warm peripheries, tachycardia, atrial fibrillation, hair loss) or hypothyroidism (bradycardia, dry thin hair, dry coarse skin)
Investigations
• Thyroid functions tests (TSH, T4 — most patients will have a high T4 and a low TSH level, although in 5–10% of patients, thyroid orbitopathy will be associated with a euthy- roid condition) and thyroid autoantibodies (anti-TSH receptor, anti-thyroid peroxidase, anti-thyroglobulin antibodies)
• In some patients, the diagnosis is so obvious that no imaging is necessary
• CT scan with axial and coronal cuts (see Fig. 2.46): enlarged extraocular muscles, proptosis (>1/3 of eye in front of imaginary line from medial to lateral canthus), CT is preferred imaging modality for planning orbital decompression
• MRI (T2 STIR): better soft tissue resolution and used for grading disease activity, enlarged muscle bellies with sparing of the tendons
• Orthoptic review: Hess/Lees chart, field of bin- ocular single vision, field of uniocular fixation
• Serial visual evoked potentials (VEP — pro- vides objective assessment of optic nerve function — important to know that patient is euthyroid before evaluating the result, as hypothyroid patients without optic nerve com- pression can show a delay in the P100 compo-
nent of the VEP)
• Forced duction test: confirm presence and
extent of mechanical restrictions
Disease Stratification
• If TED is suspected, determine disease activ- ity and disease severity in order to assess the urgency of treatment
• Disease activity — grade disease activity using the Clinical Activity Score — CAS (Mourits et al. 1997) — at initial visit, patients are given a CAS score of 1–7, 1 point for each sign or symptom (ocular pain at rest in the last 4 weeks, ocular pain on eye movement in the last 4 weeks, eyelid swelling that is considered to be due to active TED, eyelid erythema, con- junctival injection considered to be due to active TED, chemosis, inflammation of carun- cle or plica semilunaris); At follow-up visits, add the three following criteria (increase of at least 2 mm proptosis during a period of one to three months, decrease in uniocular motility in any one direction of at least 5° during a period of one to three months, decrease in VA equiva- lent to 1 Snellen line during a period of one to three months) for a potential CAS score of 10 (1 point for each sign or symptom)
• TED is considered “active” if the CAS is 3 or more at the initial visit or 4 or more at the fol- low up visits
• Disease severity:
– EUGOGO classification scheme (Bartalena
et al. 2008):
Mild TED: lid retraction less than 2 mm, exophthalmos less than 3 mm above nor- mal, mild soft tissue involvement, transient or no diplopia, corneal exposure responsive to lubricants — insufficient to justify immunosuppressive/surgical treatment Moderate-severe TED: lid retraction at least 2 mm, exophthalmos at least 3 mm above normal, moderate to severe soft tis- sue involvement, constant diplopia — suf- ficient impact on QOL to justify immunosuppression if active or surgical intervention if inactive
Sight threatening TED: optic nerve neu- ropathy and/or corneal breakdown — war- rant immediate intervention
– NOSPECS:
No signs or symptoms Only signs no symptoms Soft tissue involvement Proptosis
EOM involvement Cornea involvement
Sight loss
Rundle’s Curve
• Depicts schematically the typical course of
disease severity with time
• Characterised by an active phase of increasing
severity, a regression phase of decreasing severity, and an inactive plateau phase
Treatment
• Achieve a euthyroid state without post-treat- ment hypothyroidism — seek consultation with an endocrinologist if the patient is not seeing one. Treatment of hyperthyroidism — carbimazole or propylthiouracil, radioactive iodine — short course of prophylactic oral ste- roid to prevent new onset or progression of TED, thyroidectomy. Treatment of hypothyroidism — levothyroxine
• Promotion of smoking cessation
• Before initiating treatment, determine where
the patient’s condition falls in the natural his- tory of the disease. Try to determine whether patient is in the “active” stage (swelling or redness of the orbital, lid, and conjunctival tis- sues — eyelids look “wet” as though you could squeeze oedema fluid out, eyelid swell- ing and any diplopia are much worse in the mornings) or “chronic” stage (morning eyelid swelling and diplopia are gone, signs of acute inflammation are no longer present, any remaining proptosis and lid retraction proba- bly will not change) of the disease
• Mild TED/CAS <3 — most patients will require only medical management during the active stage — monitor patients for corneal exposure and treat irritation with lubricating drops and ointment, elevate head of the bed to reduce morning swelling or diplopia, sun- glasses to decrease photophobia and feelings of dryness, prisms for diplopia
• Moderate-severe TED/CAS ≥3 — consider immunosuppression (systemic corticoste- roids — IV methylprednisolone or oral pred- nisolone, rituximab, etanercept, AZT) or orbital radiotherapy (2000 rad — for patients with restrictive myopathy but not for acute optic nerve compression — contraindications include history of skin cancer, age less than 35 years old)
• Sight threatening TED — admit patient, IV methylprednisolone 1 g every day for 3 days (maximum total dose of 8 g — if dose exceeds measure LFT’s as small risk of acute liver damage). Surgical decompression (fat and/or bony decompression) if the steroid therapy fails and if systemic steroid therapy is contra- indicated or has intolerable side effects.
• Surgical (decompression then strabismus sur- gery then lid surgery) — when you have con- firmed that there has been no change over 3–6 months, the patient may want to consider procedures to improve the remaining propto- sis, lid retraction, and strabismus (to correct diplopia: conservative — prisms, botulinum injection,andBangerterfoils,surgical—indi- cated when there is diplopia in primary gaze and downgaze and stable inactive TED with stable myopathy for at least 6 months)
Prognosis
• Poorprognosticfactors:smoker,male,olderage at onset, diabetes, reduced vision, rapid progres- sion at onset, longer duration of active disease
ORBITAL PSEUDOTUMOUR
Other Diagnoses to Consider
• Bacterial orbital cellulitis — patient usually sick (febrile, weak, etc.), onset usually takes place over a few days, pain usually less than with orbital pseudotumour
• Orbital haemorrhage — onset usually more sudden, with progression occurring over a few minutes, rather than hours
History
• Any pain and rate of progression — acute/ abrupt onset of pain with rapid progression occurring over hours to a day or at most two
• Past medical history is only helpful for chil- dren in whom a viral syndrome may precede the onset
Key facts about orbital pseudotumour
• Any of the orbital tissues may become infiltrated with inflammatory cells (dacryoadenitis or myositis)
• Both young and old people are affected
Examination
• Look for proptosis
• Look for periocular signs of acute inflamma-
tion predominate — lid swelling, chemosis
• Look for limited motility
• With palpation, the tissues are tense and warm,
but no distinct mass will be present. The inflamed areas are tender to touch. There are no pulsations.
Investigations
• FBC, CRP: normal
• CT scan : poorly circumscribed
(poorly defined margins) mass may be present in any orbital space, dacryoadenitis, myositis (diagnosis can usually be made clinically if the onset and pain are typical)
Management
• Rapid response to oral prednisolone (80 mg/ day) is characteristic. Treatment should be con- tinued for 6–8/52 with a tapering schedule.
Cavernous Haemangioma
History
• Any pain and rate of progression — painless
and slow progression
Examination
• Vision: not affected unless the mass pushes directly on the eye causing a hyperopic shift
• Look for proptosis: unilateral, axial
• The typical cavernous hamangioma is too far
posterior to be palpable
• There are no associated periocular signs
• Although lesion is vascular, there is low flow
so no pulsations are seen
Investigations
• CT scan: well circumscribed oval or round mass, usually in the muscle cone (intraconal)
Keys facts about cavernous haemangioma
• Most common benign orbital tumour in adults • Most common around age 40
Management
• Observation: repeat CT scan at three to four
months or sooner if any visual loss, pain or
change in proptosis occurs
• Removal via orbitotomy: if diagnosis is uncer-
tain, vision loss is present, or the patient does not want observation, excisional biopsy (removal) is recommended.
OPTIC NERVE MENINGIOMA
History
• Any pain and rate of progression — no pain, rate of progression is very slow over months to years
• Any vision loss — patient’s usually note vision loss from compression of the nerve before tumour is large enough to cause proptosis
Examination
• Look for proptosis — usually minimal at the time of presentation — if present, the propto- sis is axial
• No external signs of disease are present
• Palpation of the orbit is normal
• No abnormal pulsations of the eye are seen
• Look for optic disc swelling — may be present • Look for optociliary shunt vessels — compression of the CRA can occur so that blood flow is shunted to the retina via the ciliary vessels
Investigations
• CT scan: enlargement of the optic nerve, cal- cification of the arachnoid (parallel radiodense lines on the sides of the nerve — tram tracking)
• MRI scan: to determine extent of the tumour into the orbital apex and chi- asm — will be able to see posterior extent of the tumour without the artefact of the bones in the apex obscuring the soft tissue detail as on a CT scan
Key facts about optic nerve meningioma
• Most often seen in middle-aged adults
• Benign tumour originates in the arachnoid villi of the
• Most common benign orbital tumour in adults • Most common around age 40
meningeal sheath of the optic nerve
• Incisional biopsy: if diagnosis cannot be made clinically
Treatment
• Observation: recommended if VA is good
• Excision: debulking of an optic nerve menin- gioma cannot be done without damage to the vision, so no attempt to excise is usually done until useful vision is lost (blind eye) or the tumour is extending toward the optic canal as
seen on serial MRI examination
• Meningioma’s in patients younger than 35
behave more aggressively, suggesting that ear- lier excision should be considered
Orbital Diseases Occurring in Childhood
• Malignancy is a less common cause of proptosis
• Congenital abnormalities are more common causes — choristoma (normal tissue in an abnormal anatomic location, e.g. dermoid cyst), and hamartoma (normal tissue in abnor- mal quantity, e.g. haemangioma or glioma)
• Thyroid orbitopathy is a rare cause of propto- sis in children
• Infection is a common cause of proptosis in children
• Rhabdomyosarcoma must be considered in any child with rapidly progressive proptosis
Differential Diagnosis
• Dermoid cyst
• Capillary haemangioma
• Orbital cellulitis
• Lymphangioma
• Rhabdomyosarcoma
• Optic nerve glioma
DERMOID CYST
Other Diagnoses to Consider
• Lateral anterior dermoid: lacrimal gland mass, lipodermoid, teratoma, plexiform neurofibroma • Medial anterior dermoid: mucocele, haeman- gioma, encephalocele
• Cyst with spontaneous rupture: orbital celluli- tis, orbital pseudotumour
• Deep dermoid with mass effect: primary cra- nial nerve palsy
History
• Onset — first few months of life, deep orbital dermoid cysts, such as those originating from the sphenozygomatic suture, present later, usually in young adults
• Pain — painless
• Progression — mass increases in size very
slowly
• Diplopia — mass effect of a deep dermoid cyst
Examination
• Location of cyst (forms differentials): cyst can occur at any suture line, but it is most com- monly seen at the frontozygomatic suture line (frontonasal suture next most common)
• Palpate cyst: smooth to palpation, can be either freely moveable or attached firmly to the bone. No mass palpable for a deep orbital dermoid cyst
• Displacement of globe/proptosis: mass effect of a deep orbital dermoid cyst
• Ocular motility: deficits caused by a deep orbital dermoid cyst
Investigations
• Imaging of the typical frontozygomatic dermoid cyst in an infant is not required if you can feel around the equator of the mass, suggesting that the entire mass is outside of the orbital cavity
• If the mass is firmly fixed to the bone or you cannot feel around the mass, there may be a component of the cyst extending into the bone or in the orbit itself. Imaging is not absolutely necessary, but it may help you to plan your operation because some bone removal may be required in rare patients.
• If mass is nasal (differentials — haemangioma, encephalocele), order a scan if you are not absolutely sure that the mass is a dermoid cyst
• CT scan: well circumscribed round mass adja- cent to the bone, contents of the cyst may have the density of water or oil; occasionally one can see an interface between the oil and water lay- ers (dermoid cyst); deep orbital dermoid cyst usually diagnosed on CT (large well circum- scribedmasswithinanareaofbonemoulding to accommodate the slow growth of the cyst), as there may be no characteristics in the history or examination to make a definitive diagnosis.
Treatment
Facial photo of a patient with a lower eyelid capillary haemangioma
• Excision of cyst: rupture during removal may lead to recurrence
Key facts about dermoid cysts
• A choristoma containing skin and skin appendages such as hair and oil glands
• In utero, a bit of skin is “pinched” in a suture line where the tissue gradually forms a cyst. The lining of the cyst is normal skin. The contents of the cyst include keratin, oil and hair
• If the cyst wall does not contain skin appendages, it is called an epidermal cyst
CAPILLARY HAEMANGIOMA
Key facts about capillary haemangiomas
• The most common orbital hamartoma.
• Haemangiomas, if untreated, have three phases:
initial growth phase (ends before 6 months of age), stable phase, spontaneous involution phase (begins at 1 year of age up until age 8)
History
• Onset and pain — not present at birth but appears in the first few months of life, painless
Examination
• Look for a blush of red or blue to skin with little elevation (cutaneous haemangioma) and/ or bluish elevation with no surface vasculari- sation (subcutaneous haemangioma) on the lid/forehead
• Look for proptosis: subcutaneous portion of haemangioma may extend into the orbit caus- ing displacement of the eye inferiorly or proptosis
• Look for ptosis: any large eyelid lesion can cause ptosis
• Cycloplegic refraction: during the growth phase look for astigmatism and amblyopia
• Slight changes in size occur with crying,
probably as a result of vascular engorgement (low flow lesion so no pulsations are present)
Treatment
• Indications — amblyopia, astigmatism, or bony orbital asymmetry develops
• Intralesional steroid injection (Triamcinolone [Kenalog, Squibb] 40 mg/mL + betametha- sone 6 mg/mL) — helpful if an upper eyelid mass causes amblyopia — follow up 6 weeks post injection
• Oral prednisolone — 1–2 mg/kg/day — if a mass is in the orbit causing proptosis or if the haemangioma is very large — include paedia- trician in this treatment
• Systemic propranolol (Leaute-Labreze et al. 2015) — 3 mg/kg/day for 6 months
• Surgical excision with subsequent reconstruc- tion of the resultant skin defect
ORBITAL CELLULITIS
Key facts about orbital cellulitis
• Infection of the ethmoid sinus (sinusitis) spilling into the orbit is the usual cause
• Other causes: dacryocystitis, dental abscess, penetrating orbital trauma (septal perforation), surgical (strabismus and retinal surgery)
• Preseptal cellulitis — in younger children, in whom the orbital septum is not fully developed there is a high risk of progression and so should be treated similarly to orbital cellulitis. Unless there is an obvious cause for the preseptal cellulitis, such as an insect bite, you should consider the possibility of an ethmoid infection causing the eyelid swelling. Preseptal inflammation without evidence of a skin wound should be considered sinus in origin until proven otherwise. Order a CT scan to find out
DIFFERENTIAL DIAGNOSIS OF INFLAMMATORY PROPTOSIS
Inflammation
– Orbital inflammatory disease: onset over days or weeks, afebrile, children are more likely to have anterior/posterior uveitis, normal FBC
– Sarcoidosis: anterior/posterior uveitis, arthropathy, skin rash
– Wegener’s granulomatosis: bilateral, globe displacement with orbital mass, nasal blockage/discharge/bleeds, hearing loss, pain over paranasal sinuses
–Ruptured dermoid cyst: globe displacement
• Penetrating orbital trauma
• Neoplasia:
– Benign orbital tumours — lymphangioma, haemangioma
– Malignant orbital tumours — rhabdomyo- sarcoma, leukaemia, metastatic disease
• Endocrine:
– TED: lid retraction
Classification
• Chandler classification of orbital complica- tions of sinusitis (Chandler et al. 1970):
– Class I: Inflammatory oedema (preseptal
cellulitis)
– Class II: Orbital cellulitis
– Class III: Subperiosteal abscess (SPA)
– Class IV: Orbital cellulitis
– Class V: Cavernous sinus thrombosis
History
• Any pain and rate of progression — proptosis develops over a few days with associated pain
• Recent history of URTI
• History of sinus disease
• History of any dental abscess
• History of dacryocysitis
• History of trauma — septal perforation
• History of surgery — lacrimal procedure, orbi-
totomy, lid operation, strabismus operation
• History of diabetes or immunocompromised (more for adults) — fungal orbital cellulitis
Examination
• Child looks sick (unlike with orbital pseudotu- mour) — weak, tired, and febrile (check temperature)
• Mild to advanced signs of orbital inflamma- tion (similar to orbital pseudotumour) — proptosis, swollen, red, tender and warm lids, chemosis, limited extraocular movements (mechanical limitation)
• Look for optic nerve compromise — VA, RAPD, Colour vision
• Look for dacryocystitis
• Look for an insect bite/FB from trauma
Investigations
• FBC (raised WCC), CRP, Blood cultures
• CT orbits and sinus (see Fig. 3.23) — sinus disease, abscess formation in the orbit (sub- periosteal/intraorbital abscess) ± intracranial,
cavernous sinus thrombosis
Treatment
• Consult with ENT (sinus drainage) and paediatricians
• Broad-spectrum IV antibiotics and nasal decon- gestants (ephedrine) ± IV fluid: improvement should occur within 24–48 h. Daily review.
• Any Intraconal/orbital abscess should be drained
• Indications for early drainage of a SPA (Garcia and Harris 2000): age more than 9, presence of frontal sinusitis, non-medial location of SPA, large SPA, suspicious of anaerobic infection (e.g. presence of gas in abscess on CT), recur rence of SPA after prior drainage, evidence of chronic sinusitis (e.g. nasal polyps), acute optic nerve compromise, infection of dental origin
Complications Investigation
• Subperiosteal and orbital abscess
• Cavernous sinus thrombosis: CN III, IV, V1,
VI CN palsies, retinal venous dilatation +
optic disc swelling
• Meningitis
• Septicemia
• Brain abscess
• Optic neuropathy
• CRAO
Optic Nerve Glioma
History
• Pain and rate of progression: slowly progres- sive, no pain
• History of NF-1/Family history of NF-1 (first degree relative)
Examination
• Look for axial proptosis: suggests an
Intraconal mass
• Check optic nerve function: VA, RAPD,
Colour vision — optic nerve compromise
• Look for signs of NF-1: café-au-lait spots, plexiform neurofibroma, lisch iris nodules
(see Fig. 3.24), axillary/inguinal freckling • Look for optic disc swelling
Investigation
CT scan (see Figs. 2.54 and 2.56): enlarged nerve, often fusiform in shape, mass causes eccentric enlargement of the nerve, no calcification
• MRI scan: to delineate posterior extent of tumour — optic nerve tumour is characteristi- cally bright on a T2-weighted scan — chiasm can be involved in up to 50% of cases of optic nerve glioma
• Incisional biopsy: only if diagnosis is in question
Treatment
• Observation with serial MRI scans performed every 6 months or so — majority of optic nerve gliomas are benign (hamartomas) and little or no growth posteriorly along the nerve will be seen over time
• Excision: only recommended for blind eyes with disfiguring proptosis or posterior spread threatening the chiasm, usually performed through a transcranial orbitotomy, removing the entire nerve
• Chemothetrapy/radiotherapy: for chiasmal or midbrain involvement
