Retina - Other

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When a storm is brewing inside of the vitreous, how do you get to the destination safely? Before the 1995 EVS study, there was no clear consensus on how to utilize vitrectomy and IV antibiotics for patients with post-op endophthalmitis. Therefore, the EVS study sought to define a treatment protocol for these scary cases. In the study, 420 patients with clinical evidence of endophthalmitis within 6 weeks after cataract surgery or secondary intraocular lens implantation were randomly assigned to four groups with combinations of pars plana vitrectomy PPV or no PPV, and treatment with or without systemic antibiotics.

Key Points:

• Systemic antibiotics may not be necessary and increase cost, length of stay, and toxic side effects
• Routine PPV is not necessary for patients with better than light perception (LP) vision at presentation
• PPV is beneficial for patients presenting with LP or worse vision, leading to better visual outcomes and reduced adverse outcomes 

Overall, EVS established an LP cutoff for routine PPV in post-op endophthalmitis. If a patient can see HM, you can wave them goodbye instead of taking straight to the OR.

In the days before anti-VEGF, what did retina docs do?This 1984 trial sought to answer three questions when it comes to managing patients after branch vein occlusion. 1) Can photocoagulation prevent the development of neovascularization (NV)? 2) Can photocoagulation prevent vitreous hemorrhage (VH)? 3) Can photocoagulation improve visual acuity in eyes with macular edema reducing vision to 20/40 or worse? To do so, 502 eyes were categorized into four groups: I. eyes at risk for development of NV; II. eyes at risk for development of VH; III. Eyes at risk for vision loss; X. eyes at high risk for NV.

Key Points:  

• In Group I, treatment reduced rates of NV development (22% vs. 12%)
• In Group II, treatment reduced rates of VH (29% vs. 61%)
• For Group III, treatment led to greater visual improvement than control eyes

Overall, the BVOS is a landmark study because it highlighted the important role of argon laser photocoagulation in the prevention of development of neovascularization and vitreous hemorrhage in eyes with branch vein occlusion. Further, treatment with argon laser photocoagulation is recommended for those with branch vein occlusion and visual acuity reduced from macular edema to 20/40 or below. With treatment, improvement of visual acuity is more likely than without laser treatment. 

Does prophylactic photocoagulation help central retinal vein occlusion (CRVO) outcomes? This phase 3 randomized control trial in 1995 analyzed patients who had CRVO within the last year and split them into Group N (181 patients with nonperfused CRVO with no neovascularization) and Group M (151 patients with 20/50 or worse visual acuity and macular edema secondary to CRVO). The primary outcome for Group N was regression of the development of neovascularization after prophylactic pan-retinal photocoagulation (PRP). The primary outcome for Group M was visual acuity after macular grid laser therapy at 3 years. 

Key Points:

• Group N: Prophylactic PRP reduced proportion of patients who developed iris or angle neovascularization, but this difference was not statistically significant (35% vs. 20%, OR 0.6, P = 0.17) after adjusting for baseline characteristics
• Group N: Iris and angle neovascularization was more successfully treated by PRP in patients who had not had prophylactic PRP (56% vs. 22%, OR 4.5, P = 0.02)
• Group M: There was no statistically significant difference in visual acuity in those who received grid laser versus those who received no treatment at 3 years. 

Overall, the CVOS study is a landmark study because it did not support prophylactic photocoagulation being utilized for the treatment of CRVO. While treatment regimens have changed since the development of Anti-VEGF agents and improved clinical imaging (OCT), the CVOS remains one of the important foundational studies in the field.

Some risks are worth taking…but not cardiovascular risk. The Eye Disease Case-Control Study looked to describe potential risk factors associated with central retinal vein occlusion in this prospective, case-control study.

Key Points:

• Multivariate analysis revealed an associated increased risk of CRVO in individuals with systemic hypertension, diabetes mellitus requiring treatment, and decreased physical exercise
• Risk for ischemic CRVO risk was significantly increased in patients with cardiovascular disease, history of diabetes mellitus, and hemoglobin A1C greater than 6.3%
• Postmenopausal women had a decreased risk of CRVO when using exogenous estrogen replacement  

In short, individuals with cardiovascular risk factors such as systemic HTN, increased blood sugar levels, and less physical exercise are more at risk of CRVO, especially the ischemic type. Of note, women who used postmenopausal estrogens were at a decreased risk of CRVO, suggesting a potential protective role of exogenous estrogen in this population. .

Corticosteroids reduce macular edema in patients with retinal vein occlusion? SCORE! The Standard Care vs Corticosteroid for Central Retinal Vein Occlusion (SCORE-CRVO) sought to determine the optimal treatment for vision loss associated with macular edema secondary to perfused central retinal vein occlusion (CRVO). 271 patients from 66 clinical sites were randomized to three groups: observation (n=88), 1mg intravitreal triamcinolone (n=92), 4mg intravitreal triamcinolone (n=91). Participants were retreated at 4-month intervals for 36 months. 

Key Points:

• The likelihood of a 15 letter gain in visual acuity at 1 year was five times greater with 1mg intravitreal triamcinolone (95% CI, 1.8-14.1; P=.001) and 4mg intravitreal triamcinolone (95% CI, 1.8-14.4; P=.001) compared to the observation group
• Unlike visual acuity, no significant difference was found in retinal thickness between groups at 12 months
• There was a dose-dependent relationship to the need of initiating IOP-lowering medications with triamcinolone (41% in the 4-mg group and 7% in the 1-mg group) compared with the standard-care group (2%)

Overall, the SCORE-CRVO is a landmark study because it led to a major shift in the treatment of vision loss associated with macular edema secondary to CRVO. Prior to this study, there was no proven, effective treatment for this condition and the standard of care was observation. The results demonstrate both 1-mg and 4-mg intravitreal triamcinolone had better visual acuity outcomes over 12 months compared to the untreated natural course of disease. Given the safety profile of the low dose, particularly with respect to glaucoma and cataract, 1-mg intravitreal triamcinolone became the preferred treatment of macular edema in patients with CRVO. Shortly after this study, however, another set of Landmark studies (BRAVO & CRUISE) enlightened us to even more effective treatment options.

Keep your friends close, but your anti-VEGF injections closer… The BRAVO and CRUISE trials looked to find the best course of treatment for macular edema in the setting of branch and central retinal vein occlusions. Prior to this, laser therapy had proven to be ineffective and patients were simply observed with little hope in visual improvement. In the BRAVO and CRUISE trials, patients with macular edema following BRVO (n=397) and CRVO (n=392) were randomized to receive monthly intravitreal injections of 0.3 or 0.5 mg of ranibizumab or sham injections.

Key Points:

• For BRVO, an increase in at least 15 letters in BCVA at 6 months was seen in 55.2% (0.3 mg) and 61.2% (0.5 mg) of patients compared to only 28.8% in the placebo arm; for CRVO, the respective groups yielding 46.2% (0.3 mg), 47.7% (0.5 mg), and 16.9% (placebo)
• Central foveal thickness at 6 months following BRVO/CRVO had decreased by a mean of 337/434 mircons (0.3 mg) and 345/452 microns (0.5 mg) in the ranibizumab groups compared to 158/168 mircons in the placebo grou
• The BRAVO trial saw more placebo patients (54.5%) receive rescue grid laser compared with the 0.3 mg (18.7%) and 0.5 mg (19.8%) ranibizumab groups

The importance of this study was showing that anti-VEGF injections were effective in treating macular edema following retinal vein occlusions leading to marked improvement in visual acuity while still maintaining a very low risk of complications.

Welcome to the era of gene therapy. In this phase 3 clinical trial, 31 patients (age 3 and up) with biallelic RPE65 mutations and retinal dystrophy were randomized to either control (n=10) or intervention group (n=21) to receive bilateral subretinal injection of 1.5x1011 vg of AAV2-hRPE65v2 gene augmentation therapy. The primary outcome was ability to navigate low-to-medium light conditions, measured by multi-luminance mobility testing score.

Key Points:  

• Intervention led to rapid and significant as the control group improved by 0.2 (SD 1.0) and intervention group by 1.8 (1.1) (95% CI 0.72-2.41, p=0.0013). 
• Light sensitivity improved over 2 log units (p=0.0004) and Goldmann visual field nearly doubled (p=0.0059) for the intervention group
• Safety outcomes in the 1-year observation period demonstrated no vector-related adverse events and adverse ocular events related to the procedure were transient, mild, or treatable  

This study demonstrated efficacy of voretigene neparvovec gene augmentation via improved functional vision in RPE65-mediated inherited retinal dystrophy. As the first study of its kind of a gene therapy for a genetic disease, this landmark trial additionally provided a foundation that has since been applicable to the treatment of other inherited vision disorders. For more on this interesting topic, listen to this podcast where Kathy High, one of the  leaders of the RPE65 gene therapy phase 3 trial discusses this trial.

 When things seem blurry, a PIVOT in your vision can bring them back into focus. The aim of this study was to evaluate and compare the results of pneumatic retinopexy (PnR, n=77) and pars plana vitrectomy (PPV=73) as treatment options for primary rhegmatogenous retinal detachment (RRD) involving the superior retina. 

Key Points:  

• ETDRS scores for PnR were better than PPV by 4.9 letters at 12 months (79.9 ±10.4 letters vs. 75.0 ±15.2 letters; P=0.024).
• Vertical metamorphopsia scores were superior for the PnR group compared with the PPV group at 12 months (0.14±0.29 vs.0.28±0.42; P=0.026). 
• Primary anatomic success at 12 months was achieved by 80.8% of patients undergoing PnR versus 93.2% undergoing PPV (P=0.045), with 98.7% and 98.6%, respectively, achieving secondary anatomic success.

Overall, the PIVOT landmark study demonstrated that pneumatic retinopexy is recommended as the initial treatment for eligible superior RRDs, as it offers superior visual acuity, fewer metamorphopsias, and a lower complication rate compared to vitrectomy.