Vitrectomy for diabetic macular edema: a systematic review and meta-analysis.

OBJECTIVE: To systematically review, and perform meta-analysis on, the available data regarding the efficacy of vitrectomy for diabetic macular edema. DESIGN: Systematic review and meta-analysis of published randomized controlled trial data. METHODS: We searched PubMed and the Cochrane database for randomized, controlled trials investigating vitrectomy for diabetic macular edema. Structural (foveal thickness) and functional (visual acuity) outcomes were used as the primary outcome measures. RESULTS: Eleven studies met the criteria for inclusion in this review: these studies were heterogenous in their experimental and control interventions, follow-up period, and eligibility criteria. Seven studies compared vitrectomy with the natural history of diabetic maculopathy, with laser, or with intravitreal corticosteroid injection. Four studies compared vitrectomy with internal limiting membrane peeling to vitrectomy alone. One of the latter 4 studies was the only to investigate vitrectomy in patients with vitreomacular traction. Meta-analysis suggests a structural, and possibly functional, superiority of vitrectomy over observation at 6 months. Vitrectomy also appears superior to laser in terms of structural, but not functional, outcomes at 6 months. At 12 months, vitrectomy offers no structural benefit and a trend toward inferior functional outcomes when compared with laser. CONCLUSIONS: There is little evidence to support vitrectomy as an intervention for diabetic macular edema in the absence of epiretinal membrane or vitreomacular traction. Although vitrectomy appears to be superior to laser in its effects on retinal structure at 6 months, no such benefit has been proved at 12 months. Furthermore, there is no evidence to suggest a superiority of vitrectomy over laser in terms of functional outcomes

Endophthalmitis following intravitreal injection versus endophthalmitis following cataract surgery: Clinical features, causative organisms and post-treatment outcomes

AIMS: To describe and compare the causative organisms, clinical features and visual outcomes of endophthalmitis following intravitreal injection (IVI) to endophthalmitis following cataract surgery. METHODS: Patient population and setting: A retrospective case series of patients with acute endophthalmitis following either cataract surgery or IVI presenting to a tertiary referral centre--Sydney Eye Hospital--between 2007 and 2010. MAIN OUTCOME MEASURES: (1) identification of the causative organism; (2) time to presentation; (3) odds of improvement in visual acuity (VA) following treatment; (4) odds of final VA of counting fingers (CF) or less and (5) odds of enucleation. RESULTS: Of the 101 patients in our study, 48 had preceding cataract surgery and 53 had preceding IVI. There was an increased incidence of Streptococcus spp. endophthalmitis in post-IVI cases (24.53% vs 6.25%; OR 5.85; p=0.022). Endophthalmitis following IVI had increased likelihood of a final VA of CF or less (OR=6.0; p<0.01), decreased likelihood of any improvement in acuity following treatment (OR=0.13; p<0.01) and an increased likelihood of presenting within a week of the procedure (OR=3.93; p<0.01). Endophthalmitis caused by Streptococcus spp. was associated with increased likelihood of a final VA of CF or less (OR=10.2; p<0.01), decreased likelihood of any improvement in acuity following treatment (OR=0.06; p<0.01) and increased likelihood of enucleation (OR=17.11; p<0.01). CONCLUSIONS: Endophthalmitis following IVI is associated with an increased incidence of Streptococcus spp. infection, earlier presentation and poorer visual outcomes when compared with endophthalmitis following cataract surgery

Endophthalmitis following intravitreal injection versus endophthalmitis following cataract surgery: clinical features, causative organisms and post-treatment outcomes.

AIMS: To describe and compare the causative organisms, clinical features and visual outcomes of endophthalmitis following intravitreal injection (IVI) to endophthalmitis following cataract surgery. METHODS: Patient population and setting: A retrospective case series of patients with acute endophthalmitis following either cataract surgery or IVI presenting to a tertiary referral centre--Sydney Eye Hospital--between 2007 and 2010. MAIN OUTCOME MEASURES: (1) identification of the causative organism; (2) time to presentation; (3) odds of improvement in visual acuity (VA) following treatment; (4) odds of final VA of counting fingers (CF) or less and (5) odds of enucleation. RESULTS: Of the 101 patients in our study, 48 had preceding cataract surgery and 53 had preceding IVI. There was an increased incidence of Streptococcus spp. endophthalmitis in post-IVI cases (24.53% vs 6.25%; OR 5.85; p=0.022). Endophthalmitis following IVI had increased likelihood of a final VA of CF or less (OR=6.0; p&lt;0.01), decreased likelihood of any improvement in acuity following treatment (OR=0.13; p&lt;0.01) and an increased likelihood of presenting within a week of the procedure (OR=3.93; p&lt;0.01). Endophthalmitis caused by Streptococcus spp. was associated with increased likelihood of a final VA of CF or less (OR=10.2; p&lt;0.01), decreased likelihood of any improvement in acuity following treatment (OR=0.06; p&lt;0.01) and increased likelihood of enucleation (OR=17.11; p&lt;0.01). CONCLUSIONS: Endophthalmitis following IVI is associated with an increased incidence of Streptococcus spp. infection, earlier presentation and poorer visual outcomes when compared with endophthalmitis following cataract surgery

Pars plana vitrectomy versus combined pars plana vitrectomy-scleral buckle for secondary repair of retinal detachment.

BACKGROUND AND OBJECTIVE: To investigate the optimal technique for repairing recurrent rhegmatogenous retinal detachments. PATIENTS AND METHODS: A 2-year retrospective review of recurrent rhegmatogenous retinal detachments by 23-gauge pars plana vitrectomy (PPV) or combined 23-gauge PPV with encircling scleral buckling was performed. The primary outcome was anatomical success. The secondary outcome was the likelihood of achieving a final best corrected visual acuity of 6/12 or better at 6-month follow-up. RESULTS: Anatomical success was achieved in 65.2% (95% CI, 53.4% to 75.4%) of the PPV group versus 74.3% (95% CI, 57.9% to 85.8%) of the PPV-scleral buckling group with one additional procedure (not statistically significant). There was no significant difference in the likelihood of achieving a final acuity of at least 6/12 between groups at 6-month follow-up. CONCLUSION: The results of our study do not demonstrate a superiority of method of primary repair, or of one method of secondary repair, over another

Pars plana vitrectomy versus combined pars plana vitrectomy-scleral buckle for secondary repair of retinal detachment.

BACKGROUND AND OBJECTIVE: To investigate the optimal technique for repairing recurrent rhegmatogenous retinal detachments. PATIENTS AND METHODS: A 2-year retrospective review of recurrent rhegmatogenous retinal detachments by 23-gauge pars plana vitrectomy (PPV) or combined 23-gauge PPV with encircling scleral buckling was performed. The primary outcome was anatomical success. The secondary outcome was the likelihood of achieving a final best corrected visual acuity of 6/12 or better at 6-month follow-up. RESULTS: Anatomical success was achieved in 65.2% (95% CI, 53.4% to 75.4%) of the PPV group versus 74.3% (95% CI, 57.9% to 85.8%) of the PPV-scleral buckling group with one additional procedure (not statistically significant). There was no significant difference in the likelihood of achieving a final acuity of at least 6/12 between groups at 6-month follow-up. CONCLUSION: The results of our study do not demonstrate a superiority of method of primary repair, or of one method of secondary repair, over another

Syphilitic retinitis and uveitis in HIV-positive adults.

BACKGROUND: The incidence of new infection with syphilis is increasing, particularly in men who have sex with men, with HIV co-infection common. There has been a corresponding increase in ophthalmic manifestations that can be varied in presentation. METHODS: Thirteen consecutive patients with syphilitic uveitis presenting to two ophthalmic departments in Sydney are described. RESULTS: Twelve patients were male, of whom 10 were homosexual and six HIV-positive. Peripheral retinitis with panuveitis was the commonest ophthalmic presentation (n = 7, 54%), and six cases were initially treated with vitreous tap and intravitreal foscarnet as a precaution in case of viral retinitis. Retinitis was present in six of six (100%) HIV-positive and only one of seven (14%) HIV-negative patients (χ² 10.6, P &lt; 0.01). Other ophthalmic presentations included anterior uveitis, vitritis, multifocal choroiditis, scleritis and papillitis. All patients responded to 10-14 days' intravenous penicillin with good final visual outcomes (6/12 or better in all eyes). CONCLUSIONS: This case series reinforces the importance of considering syphilis in the differential diagnosis of many ocular presentations, but in particular retinitis. Retinitis appears to be the predominant presentation in HIV-infected individuals, suggesting that HIV infection may somehow modulate the disease

Macular Atrophy in Neovascular Age-Related Macular Degeneration A Randomized Clinical Trial Comparing Ranibizumab and Aflibercept (RIVAL Study)

PURPOSE: To investigate differences in the development of macular atrophy (MA) over 24 months between treat-and-extend (T&E) ranibizumab and aflibercept in patients with neovascular age-related macular degeneration (nAMD). DESIGN: A phase 4 randomized, partially masked, multicenter study. PARTICIPANTS: Individuals 50 years of age or older diagnosed with active, treatment-naïve subfoveal choroidal neovascularization secondary to nAMD with baseline best-corrected visual acuity (BCVA) of 23 logarithm of minimum angle of resolution letters or more. METHODS: Patients were randomized 1:1 to receive either intravitreal injections of ranibizumab 0.5 mg or aflibercept 2.0 mg and were treated according to the same reading center-guided T&E regimen after 3 initial monthly injections. MAIN OUTCOME MEASURES: The primary outcome was mean change in square root area of MA from baseline to month 24. Key secondary outcomes included number of injections and mean change in BCVA from baseline to months 12 and 24. RESULTS: Two hundred seventy-eight patients were included in the analysis (ranibizumab 0.5 mg, n = 141; aflibercept 2.0 mg, n = 137). Mean change in square root area of MA from baseline to month 24 was +0.36 mm (95% confidence interval [CI], 0.27-0.45 mm) for ranibizumab and +0.28 mm (95% CI, 0.19-0.37 mm) for aflibercept (treatment difference, +0.08 mm [95% CI, -0.05 to 0.21 mm]; P = 0.24). The proportion of patients with MA increased from 7% (10/141) to 37% (43/117) for ranibizumab and from 6% (8/137) to 32% (35/108) for aflibercept from baseline to month 24. The average number of injections received per year was similar between both groups: 9.6 (95% CI, 9.2-10.0) for ranibizumab and 9.5 (95% CI, 9.1-9.9) for aflibercept. The mean change in BCVA from baseline to month 24 was +6.6 letters (95% CI,4.7-8.5 letters) for the ranibizumab group and +4.6 letters (95% CI, 2.7-6.6 letters) for the aflibercept group ( P = 0.15). Rates of adverse events (AEs) were similar between both groups. CONCLUSIONS: No significant differences in the rate of development or growth of MA over 24 months were observed between ranibizumab and aflibercept in nAMD patients treated using an identical T&E regimen

Effects of switching from ranibizumab to aflibercept in eyes with exudative age-related macular degeneration

AIMS: To examine 12-month outcomes of eyes switching from intravitreal ranibizumab to aflibercept for neovascular age-related macular degeneration (nAMD). METHODS: Database observational study of eyes with nAMD tracked by the Fight Retinal Blindness outcome registry that received ranibizumab for at least 12 months before switching to aflibercept and followed for at least 12 months after the switch. Visual acuity (VA) recorded at 12 months after the switch was analysed using locally weighted scatterplot smoothing curves. Lesion activity was graded according to a prospectively identified definition. Main outcomes were change in VA and treatment intervals 12 months after the treatment switch. Secondary outcomes included change in activity grading, effect of duration of treatment before switching and analysis of eyes that switched back. RESULTS: A total of 384 eyes switched from ranibizumab to aflibercept after a mean duration of 39.8 months on the original treatment. The mean VA did not change from the time of switching treatment (63.4, SD 15.9 logarithm of the minimum angle of resolution letters) to 12 months later (63.3, SD 16.7). While 10% of eyes gained 10 or more letters 12 months after the switch, 13% lost the same amount. The mean number of injections decreased by around one injection in the 12 months after switching (p<0.001), with a decrease in the proportion of choroidal neovascular membrane lesions that were graded as active. Eyes that had been treated for the longest time (49 or more months) before switching had worse vision at the point of switch but neither change in VA nor treatment interval was different between groups. The small proportion (6.9%) of eyes that switched back again to ranibizumab had already lost a mean of 5.2 letters from the first switch to the switch back and continued to lose vision at a similar rate for at least 6 months. CONCLUSIONS: The mean VA of eyes that switched treatments from ranibizumab to aflibercept was not different 12 months later. There was a modest increase in treatment intervals and a somewhat greater proportion of eyes that were graded as inactive after the switch

Nitration of tyrosines in complement factor H domains alters its immunological activity and mediates a pathogenic role in age related macular degeneration

Nitrosative stress has been implicated in the pathogenesis of age related macular degeneration (AMD). Tyrosine nitration is a unique type of post translational modification that occurs in the setting of inflammation and nitrosative stress. To date, the significance and functional implications of tyrosine nitration of complement factor H (CFH), a key complement regulator in the eye has not been explored, and is examined in this study in the context of AMD pathogenesis. Sections of eyes from deceased individuals with AMD (n = 5) demonstrated the presence of immunoreactive nitrotyrosine CFH. We purified nitrated CFH from retinae from 2 AMD patients. Mass spectrometry of CFH isolated from AMD eyes revealed nitrated residues in domains critical for binding to heparan sulphate glycosaminoglycans (GAGs), lipid peroxidation by-products and complement (C) 3b. Functional studies revealed that nitrated CFH did not bind to lipid peroxidation products, nor to the GAG of perlecan nor to C3b. There was loss of cofactor activity for Factor I mediated cleavage of C3b with nitrated CFH compared to non-nitrated CFH. CFH inhibits, but nitrated CFH significantly potentiates, the secretion of the proinflammatory and angiogenic cytokine IL-8 from monocytes that have been stimulated with lipid peroxidation by-products. AMD patients (n = 30) and controls (n = 30) were used to measure plasma nitrated CFH using a novel ELISA. AMD patients had significantly elevated nitrated CFH levels compared to controls (p = 0.0117). These findings strongly suggest that nitrated CFH contributes to AMD progression, and is a target for therapeutic intervention