Macular Photocoagulation study: Purpose: To evaluate laser treatment of CNV through three sets of RCTs 1) Argon for extrafoveal CNV in the prevention or delay of central vision loss in three underlying conditions (AMD, POH, and INVM) 2) Kryton red photocoag for parafoveal CNV beneficial in the prevention or delay of visual acuity in patients with three underlying conditions (AMD, POH, and INVM; each with separate trials). 3) Does laser photocoagulation prevent or delay of further visual acuity loss in patient with new or recurrent CNV under the center of the FAZ. In each RCT of each MPS group, focal laser photocoagulation was compared to observation without treatment - Visual symptoms attributable to macular lesion (e.g. decreased VA, Amsler grid distortion) - Visible, well-demarcated hyperfluorescence consistent with classic CNV on FA - Eligibility criteria for each condition: o AMD: >50 years old, drusen in macula in >1 eye o POH: >18 years old, one characteristic histo spot in >1 eye o INVM: >18 years old, no evidence of AMD, POH, angioid streaks, high myopia, DR, or other identifiable cause of CNV - Additional eligibility criteria for each study: o Argon Study: Clinical serous RD with diffuse area of leakage and discrete extrafoveal CNV, VA>20/100 in study eye o Krypton Study: CNV with blood/pigment extending into the CNV; posterior border of CNV extend as close as 1 micron to FAZ center; VA>20/400 o Foveal Study: AMD patients only. FA showing leaking CNV extending under center of FAZ, or CNV consisting of old laser treatment scar and contiguous leaking CNV within 150 microns from center of FAZ. New, never-treated subfoveal lesions 20/230. Results: Argon Study: All trials (AMD, POH, INVM) halted early due to dramatic reduction in severe VA loss with argon laser treatment Krypton Study: Beneficial effect for krypton red laser treatment in eyes with AMD, most pronounced in normotensive patients (not apparent among pts with HTN). POH patients with significant benefit from krypton red laser Results in INVM patients were intermediate between AMD and POH. Foveal Study: Generally, eyes with AMD and subfoveal CNV benefitted from laser Initially, laser-treated eyes had immediately lost more vision than observed eyes; this loss was similar to the untreated group at 12 months Conclusions: For patients with well-demarcated classic CNV from AMD, POH, or INVM, treatment with laser photocoagulation, performed according to MPS guidelines, had better visual prognosis Likewise, patients with extrafoveal and juxtafoveal CNV from AMD, POH, or INVM had better visual prognosis with laser photocoagulation. Eyes with AMD and subfoveal CNV: Eyes with smaller lesion and worse initial VA had greater and earlier benefits of laser treatment Eyes with large subfoveal CNV lesions and good initial VA are not good candidates for focal laser photocoagulation
Diabetic Retinopathy Study (DRS) Does PRP (argon or xenon arc) prevent severe vision loss in eyes with diabetic retinopathy? Patients were included in the study if they had PDR in at least one eye or severe NPDR in both eyes, and had VA of 20/100 or better in each eye. Severe NPDR was defined as the presence at least 3 of the following: 1. Cotton wool spots 2. Venous beading 3. Intraretinal microvascular abnormalities (IRMA) in at least 2 contiguous overlapping photographic fields 4. Moderate-to-severe retinal hemorrhages and/or MA’s Patients were excluded if they had undergone previous PRP or had a macula-threatening TRD. This was a randomized, prospective multicenter clinical trial. 1742 study subjects were enrolled. One eye from each subject was randomly assigned to PRP and the other eye assigned to no PRP. The PRP eyes were randomized to either argon blue-green laser (800-1600, 500 micron spots) or xenon arc (200-400, 4.5 degree spots). The primary outcome measure was severe vision loss, defined as VA < 5/200 on two consecutive follow-up exams, 4 months apart. RESULTS: PRP reduced the risk of severe vision loss by at least 50% as compared to untreated control eyes. The greatest benefit was seen in eyes with high-risk PDR. Study follow-up was over 5 years. High-risk PDR was defined as any one of the following: 1. NVD ≥ 1/3 disc area 2. Any NVD with vitreous hemorrhage 3. NVE ≥ ½ disc area with vitreous hemorrhage High-risk PDR was also defined as three or more of the following high-risk characteristics (HRC’s): 1. Presence of vitreous hemorrhage or pre-retinal hemorrhage 2. Presence of any active neovascularization 3. Location of neovascularization on or within one disc diameter of the optic disc 4. NVD > 1/3 disc area or NVE > ½ disc area Eyes with high-risk PDR had significantly greater risk of severe visual loss and demonstrated the greatest benefit from PDR. No clear benefit was demonstrated for PRP in eyes with severe NPDR or in eyes with PDR without high-risk characteristics. Risks of treatment include small reductions in visual acuity or visual field. Harmful effects of argon laser treatment were less than those seen with xenon arc treatment. In the argon laser treatment group, a decrease in VA of 1 or more lines was seen in 11% of eyes; visual field loss was seen in 5%. CONCLUSIONS: PRP reduces the risk of severe vision loss compared with no treatment in eyes with high-risk PDR. Eyes with high-risk PDR should receive prompt treatment with PRP. Eyes with two or fewer high risk characteristics (HRC’s) still benefit from PRP, but the benefit is small and risks of treatment may outweigh the benefits. However, consider earlier treatment with PRP for older-onset diabetic patients.
TAP +VIM + VIP
Treatment of AMD with PDT: AMD and subfoveal classic CNV and vision 20/50 - 20/200. q3mos visits. Stable or improved vision at 12 mos: 61% treated 46% placebo, 24mos 53% treated 37% placebo Study showed that predominantly classic lesions derived greatest benefit. VIM: Visudyne in minimally classic CNVM
VIP: PDT for all types of CNVM
Defn: Classic CNVM
IVFA description: area of bright fairly uniform hyper fluorescence early in FA that inesifies throughout transit and leaks late obscuring the boundaries of the lesion
Defn: Predominantly Classic CNVM, minimally classic and occult with no classic.
Predom Classic: Classic CNV occupies more than 50%, Minimally classic: 1-49% is classic occult with no classic: duh.
Defn: Occult CNVM
2 types: Fibrovascular PED: irregular elevation of RPE with stippled or granular fluorescence. progressive leakage from lesion in a stipped fashion that is not as uniform as classic CNV. Late leakage from an undetermined source refers to regions not associated with other CNV on FA that leak late.
Comparison of lucentis to PDT for predominantly classic CNVM.
The Branch Vein Occlusion Study (BVOS) was a multi-center, randomized, controlled trial to determine the efficacy of: (1) Argon macular grid laser in treating macular oedema secondary to branch vein occlusion (reference 1) (2) Sectoral argon scatter PRP in the distribution of the vein occlusion for prevention of neovascularisation and vitreous haemorrhage (reference 2) Outcome 1 - Efficacy of Macular Grid Laser: Results were published in American Journal of Ophthalmology (see reference 1). Patients were included if there was documented branch vein occlusion, visual acuity was 20/40 or less and there was angiographic evidence of macular oedema. Patients were randomly assigned to treatment or control (no treatment) arms. In the treatment group, burns of 50-100 micrometers in diameter with exposure of 0.05 to 0.1 seconds were applied in a grid pattern to the macula - with burns no closer to the fovea than the edge of the foveal avascular zone and extending no further than the arcades. Repeat treatments were performed as necessary. The primary outcome was the percentage of patients gaining at least 2 lines of Snellen acuity from baseline and maintaining this improvement for 2 consecutive visits. The results: 139 eyes included in study with a mean follow-up of 3 years. The gain of at least two lines of visual acuity from baseline maintained for two consecutive visits was significantly greater in treated eyes (P = .00049, logrank test). The results of the BVOS trial established macular grid laser as the Gold-Standard treatment for macular oedema due to branch retinal vein occlusions for the better part of 2 decades. Recent evidence suggests that newer treatment modalities - such as intra-vitreal steroids and anti-VEGF agents - may be more efficacious than laser in this condition. Outcome 2 - Efficacy of Sectoral PRP: Results were published in the Archives of Ophthalmology (reference 2). Patients were included if they had documented branch vein occlusion with or without neovascularisation and were randomly assigned to treatment or control groups. In the treatment group, sectoral PRP was performed in the region of distribution of the affected vein. 100 to 400 laser burns were applied with spot size 200 to 500 microns in diameter and exposure 0.1 to 0.2 seconds, avoiding the fovea and optic disc. The results were as follows: In the 319 eyes without neovascularisation, treated eyes developed significantly less neovascularisation.
What is PDT and how does it work
photodynamic therapy 2 step process involving the administration of a photosensitizing drug(vertporfin) followed by application of light to a particular tissue.
A laser with a wavelength appropriate for the particular drug causes exitation of the vertporfin molecule which subsequently excited nearby oxygen molecules creating free radicals which result in thrombosis and coagulation of vasculature.
C(500), E(400), Beta catorene(15mg) Zinc (80mg *now down to 25mg, and 2 mg Copper) Now with AREDS 2 they have added Lutein 10mg and Xeaxanthin 2 mg (also, in AREDS 2, Beta carontene was removed and Omega-3s (350 DHA and 650 EDA) were not found to be helpful)
What is moderate vision loss (ADREDS)
ETDRS - 3 lines or 15 letters
What is High risk (AREDS)
Intermediate AMD in both eyes or advanced AMD in one eye - these people should be on vitalux
Define Mild AMD
Many small drusen or some intermediate drusen mild pigmentary change
Define intermediate AMD
Lots of intermediate drusen and non central GA
vision loss 20/32 due to AMD either CNV or central GA
What are the three FA findings in CSCR
smoke stack , diffuse, expansile dot.
Expansile dot is the most common and smoke stack only occurs 10-15% of the time
What features make you suspicious that a nevus will evolve into melanoma
orange pigment, symptomatic, thickness > 2mm, juxtapapillary, SRF, visual symptoms.
Atypical serpiginous with variable FAF what should you rule out
ETDRS - what are the two outcomes
Does scatter photocoag reduce progression of retinopathy?
Does focal laser improve macular edema.
Treat CSME with focal laser reduces moderate vision loss by 50%,
Any thickening within 500um, HE within 500um assoc c/ thickening, thickening of 1 disc are within 1dd of the fovea
What arden ratio defines Best's
Signs in X-Linked Juvinille retinoschisis
schisis in NFL (OPL in senile schisis)
no FA leakage (other things that do this - nicotinic acid, goldman favre, CSNB)
electronegative ERG (CSNB, x-linked retinoschesis, CRAO, sometimes CRVO)
Cluster of grapes under/in the retina?
retinal cavernous hemangioma
- cluster of grapes
- benign, non syndromic
- differs from retinal capillary hemangioma: associated with VHL
- then there are choroidal cavernous hemangioma: sturge-webber
What does choroiditis look on FA?
Early hypofluorescence with late staining in the same areas
What does APMPPE look like?
choroidits on FA: early hypofluorescence, late staining
Punched out whitish, deep lesions under the retina
How do you tell polypoidal from regular wet AMD?
Polypoidal shows up better on ICG with polypoidal, hyperfluorescent lesions.
How do you treat polypoidal?
If symptomatic, use combo PDT+anti-VEGF
What are the features of FEVR?
- dragged macula (traction)
- imcomplete vasculature of the periphery
-leakage of abnormal vessels
- autosomal dominant is most common, but can also be x-linked recessive
- Rx: laser the avascular retina
What is systemic or ocular features of stickler syndrome?
Pierre Robin sequence
RP-like pigmentary retinopathy
Optically empty vitreous
RD in 50%
mitral valve prolapse
What gives you an enhanced S cone (short-wavelength cones) on ERG?
Goldmann Favre disease
- S cones dominate, medium and long cones don't work
- show massive response to blue light (short cones)
- other findings: mid-peripheral pigment (looks like RP), vitreous veils and clear vitreous, foveal schisis
- autosomal recessive
How do you differentiate goldmann favre from juvenile retinoschisis?
EOG - abnormal in GF, normal in JR
EOG is only abnormal in GF, Best's, pattern dystrophy, chloroquine
When is EOG abnormal?
EOG is only abnormal in GF, Best's, pattern dystrophy, chloroquine
What is the inerhitance of choroideremia?
What did BRAVO compare?
for BRVO, sham vs lucentis (low and high dose) in patients with macular edema
- old standard of care was macular grid laser from BVOS
What is BVOS?
Macular edema > 3 months in BRVO, they did grid laser
What did CVOS show?
No benefit from grid laser
Standard of care became: do nothing.
Vascular occlusion studies?
BVOS: macular grid laser is better than nothing
CVOS: macular grid laser was not helpful
Score: steroids vs do nothing in BRVO & CRVO. Steroid is better than nothing for CRVO, but not better than grid laser in BRVO. Therefore, people started doing laser for BRVO but steroid for CRVO
What does a choroidal osteoma look like on U/s?
B-scan: hyperreflective with shadow behind it
Amelanotic mass, most commonly around the nerve
What is the cause of vision loss? --> CNV
Differential of retinal vasculitis
Behcet, lupus, wegner, takayasu, GCA, poly arteritis nodosum, etc
Diagnostic criteria of Behcet
HLA-51 is not part of the criteria
4 major criteria:
- ocular inflammation
- erythema nodosum
- oral ulcers
- gential ulcers
LOOK IT UP, they keep changing :)
Combined Hamartoma of the retina and RPE
Associated with NF2
What other things are assoc with NF2: PSC, combined hamartoma of the retina and RPE,
bilateral acoustic neuromas.
What are the b-scan features of choroidal melanoma
B scan - low internal reflectivity,
A-Scan: reduction of amplitude from front to back.
Worst cell type - epitheliod
Gyrate Atrophy - whats the deficiency,
high ornithine, low lysine
CRVO, Juv X-linked Retinoschisis, Goldmann-favre, CSNB, MAR,
Chloroquine, Stargarts, AMD, old Best's, hydroxychloroquine, old macular hole, olivopontocerebellar atrophy, cone dystrophy, achromatopsia, pattern dstrophy, seroid lipofucscinosis, central areolar choroidal dystrophy (Inheritance AD, Gene - RDS/Peripherin)
Small (1-3 mm)
Med (2.5 - 10 mm, ht < 16mm diameter) brachytherapy vs. enucleation 80% 5 year survival --> no difference
Large tumour (>10mm , > 16mm diameter) - external beam radiation then enucleation at 5 days. pre-enucleation external beam radiation doesn't change outcomes.
RP - type of dystrophy.
Will intensive therapy reduce microvasc compications of DM?
Will intesnive control of BP in patients who are newly Dx with DM and are hypertensive reduce the microvascualr complications?
Who:4209 pts with newly dx DM2 + 1148 pts with HTN and newly dx DM2 What: Conventional tx policy (diet) or intensive (sulfonylurea or insulin- w/ metformin if overweight)
Outcomes: development of any of 3 aggregate adverse outcomes (worsening DR, retinal photocoagulation, vitreous hemorrhage and worse VA).
Result: Intensive Control slowed progression of retinopathy and reduced the risk of other microvascular complications, as did intensive BP control.
Will intensive control of blood glucose slow development of DR?
YES - reduced development by 76%
Will intensive control of BG in patients with DR sow progression?
YES - slowed progresion by 54%
In Patients with mild NPDR and vision 20/200 or better.
Is Photocoagulation effective in treating DME?
Yes, focal laser decreased risk of moderate vision loss.
50-100um spot size, 0.1 sec duration (treat first outside macula and then titrate down until just below retinal greying.
increased chance of moderate vision gain and reduced retinal thickening.
Is Photocoagulation effective for treating DR?
No, though there was a small reduction in risk of severe vision loss at 6 months, early scatter laser not indicated.
Is ASA efective for preventing progression of DR?
Nope, didn't change progression, VH or Vacuity, all it did was reduce risk of cardio vascular mortality.
prospective RCT - evaluating early (1-6 mos post VH) vs late vitectomy(1 year) in eyes with VH and vision loss 5/200.
Patients with DM1, and in patients with severe PDR there was a clear benetfit of early vs. late vitrectomy but this was not evident in DM2
Treatment of BRVO-associated macular edema was evaluated in the phase III, BRAnch RetinalVein Occlusion: Evaluation of Efficacy and Safety trial (BRAVO – www.clinicaltrials.govNCT00486018).44 The BRAVO trial was a 6-month, multicenter, randomized, sham injection-controlled study, with an additional 6 months of follow-up (total 12 months). The study included a 6-month treatment period, during which subjects received monthly intraocular injections of 0.3 mg or 0.5 mg ranibizumab, or sham injections; and a 6-month observation period, during which all patients could receive monthly ranibizumab retreatment if they met prespecified functional and anatomic criteria (visual acuity ≤20/40 or OCT-derived CRT ≥ 250 μm). Study visits, including OCT imaging, were also carried out 7 days after baseline treatment.
392 subjects with BRVO-associated macular edema were enrolled.44 Key inclusion criteria included: BRVO-associated macular edema diagnosed within 12 months of study initiation, best-corrected visual acuity between 20/40 and 20/400, and OCT-derived CRT ≥ 250 μm (mean value obtained from 2 measurements using Stratus OCT). The primary efficacy outcome measure was mean change from baseline visual acuity at month 6. Secondary efficacy outcome measures included percentage of patients who gained ≥ 15 letters from baseline visual acuity at month 6. Additional, exploratory, efficacy outcomes included mean change from baseline NEI VFQ-25 composite score at month 6, and percentage of patients with visual acuity ≥20/40 at month 6. Safety outcomes included the incidence and severity of ocular and nonocular adverse events and serious adverse events.
Mean change from baseline visual acuity at month 6 – the primary endpoint of the study – was +16.6 and +18.3 letters in the 0.3 mg and 0.5 mg ranibizumab groups respectively, and +7.3 letters in the sham group (P < 0.0001 for each ranibizumab group versus sham).44 The percentage of patients who gained ≥15 letters in visual acuity at month 6 was 55.2% (0.3 mg) and 61.1% (0.5 mg) in the ranibizumab groups, and 28.8% in the sham group (P < 0.0001 for each ranibizumab group versus sham). At month 6, significantly more ranibizumab-treated patients (0.3 mg, 67.9%; 0.5 mg, 64.9%) had BCVA of ≥20/40 compared with sham patients (41.7%; P < 0.0001 for each ranibizumab group versus sham), and OCT-derived CRT had decreased by a mean of 337 μm (0.3 mg) and 345 μm (0.5 mg) in the ranibizumab groups and 158 μm in the sham group (P < 0.0001 for each ranibizumab group versus sham). An improvement from baseline in the mean NEI VFQ-25 score was observed as early as month one in ranibizumab-treated patients. At month 6, the mean change from baseline score was 9.3, 10.4, and 5.4 points in the 0.3 mg, 0.5 mg, and sham groups respectively (P < 0.05 for each ranibizumab group versus sham). Finally, the safety profile was consistent with previous phase III clinical trials of ranibizumab, and no new safety events were identified in patients with CRVO.
As the efficacy of grid laser photocoagulation for the treatment of BRVO-associated macular edema had already been demonstrated in the BVOS,14 BRAVO participants were eligible for grid laser 3 months after study entry if they had not shown evidence of substantial visual or anatomic improvement from baseline (providing there was sufficient clearing of retinal hemorrhages).44 As a result, in the BRAVO study, 54.5% of patients receiving sham injections received rescue laser therapy, whereas only 18.7% and 19.8% of the 0.3 mg and 0.5 mg ranibizumab groups required the same. Therefore, the modest improvements seen in the sham group may be attributable, at least in part, to the rescue therapy.
Good for CRVO but in BRVO resulted in cataract and High IOP
Treatment of CRVO-associated macular edema was evaluated in the phase III, Central Retinal Vein OcclUsIon Study: Evaluation of Efficacy and Safety trial (CRUISE – www.clinicaltrials.govNCT00485836).43 The CRUISE trial was a 6-month, multi-center, randomized, sham injection-controlled study, with an additional 6 months of follow-up (total 12 months). The study included a 6-month treatment period, during which subjects received monthly intraocular injections of 0.3 mg or 0.5 mg ranibizumab, or sham injections; and a 6-month observation period, during which all patients could receive monthly ranibizumab retreatment if they met prespecified functional and anatomic criteria (visual acuity ≤20/40 or OCT-derived CRT ≥250 μm). Study visits, including OCT imaging, were also carried out 7 days after baseline treatment.
392 subjects with CRVO-associated macular edema were enrolled.43 Key inclusion criteria included: CRVO-associated macular edema diagnosed within 12 months of study initiation, best-corrected visual acuity between 20/40 and 20/320, and OCT-derived CRT ≥ 250 μm (mean value obtained from 2 measurements using Stratus OCT [Carl Zeiss Meditec, Dublin, CA]). Of note, the presence of an “obvious and unequivocal” afferent pupillary defect, or previous RVO, were among the exclusion criteria. The primary efficacy outcome measure was mean change from baseline visual acuity at month 6. Secondary efficacy outcome measures included percentage of patients who gained ≥ 15 letters from baseline visual acuity at month 6. Additional, exploratory, efficacy outcomes included mean change from baseline NEI VFQ-25 (National Eye Institute Visual Functioning Questionnaire-25) composite score at month 6, and percentage of patients with visual acuity ≥20/40 at month 6. Safety outcomes included the incidence and severity of ocular and nonocular adverse events and serious adverse events.
Mean change from baseline visual acuity at month 6 – the primary endpoint of the study – was +12.7 letters and +14.9 letters in the 0.3 mg and 0.5 mg ranibizumab groups respectively, and +0.8 letters in the sham group (P < 0.0001 for each ranibizumab group versus sham).43 The percentage of patients who gained ≥15 letters in visual acuity at month 6 was 46.2% (0.3 mg) and 47.7% (0.5 mg) in the ranibizumab groups, and 16.9% in the sham group (P < 0.0001 for each ranibizumab group versus sham). At month 6, significantly more ranibizumab-treated patients (0.3 mg = 43.9%; 0.5 mg = 46.9%) had BCVA of ≥ 20/40 compared with sham patients (20.8%; P < 0.0001 for each ranibizumab group versus sham), and OCT-derived CRT had decreased by a mean of 434 μm (0.3 mg) and 452 μm (0.5 mg) in the ranibizumab groups and 168 μm in the sham group (P < 0.0001 for each ranibizumab group versus sham). An improvement from baseline in the mean NEI VFQ-25 score was observed as early as month one in ranibizumab-treated patients. At month 6, the mean change from baseline score was 7.1, 6.2, and 2.8 points in the 0.3 mg, 0.5 mg, and sham groups respectively (P < 0.05 for each ranibizumab group versus sham). Finally, the safety profile was consistent with previous phase III clinical trials of ranibizumab, and no new safety events were identified in patients with CRVO.
Significant reductions in macular edema were seen in both patient groups receiving ranibizumab at study visit Day 7; these changes were accompanied by significant visual improvements.43 Thus, the majority of CRVO-associated macular edema appears to be VEGF mediated, rather than occurring secondary to increased venous pressure. The findings of the CRUISE trial also suggest that retinal ischemia is present even in patients traditionally described as having nonischemic CRVO. Of further note, patients in the CRUISE sham injection arm demonstrated similar outcomes to those of the natural history cohort in the CVOS study; but these outcomes differed from those described in the SCORE study.16,19,43 Although the baseline visual acuity of CRUISE patients was slightly worse than that of SCORE CRVO patients (48.3 letters versus 51.0 letters respectively), CRUISE had fewer patients with large areas of capillary nonperfusion. This difference may have come about due to the exclusion of patients with an afferent pupillary defect from the CRUISE study, thus eliminating those patients with extensive capillary nonperfusion
What are the features of Choroidal Hemangioma?
Can be diffuse or focal elevated sub retinal lesion
Risk of PRD in Severe (4-2-1) in Very Severe NPDR (and two of the 4-2-1)
15% with Severe will progress
45% with very severe will progress
within one year
50% reduction of severe vision loss in patients with high risk features.
Stage 1 - peripheral vasc occlusion
2 - AV anastamosis
3 - pre retinal Sea Fan
4 - VH
5 - Tractional RD