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.
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.
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.
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.
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.
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.
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.
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.
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.