Acute Aseptic Meningitis Temporally Associated with Intravenous Polyclonal Immunoglobulin Therapy: A Systematic Review.

An acute aseptic meningitis has been occasionally observed on intravenous polyclonal human immunoglobulin therapy. Since case reports cannot be employed to draw inferences about the relationships between immunoglobulin therapy and meningitis, we conducted a systematic review and meta-analysis of the literature. Eligible were cases, case series, and pharmacovigilance studies. We found 71 individually documented cases (36 individuals ≤ 18 years of age) of meningitis. Ninety percent of cases presented ≤ 3 days after initiating immunoglobulin therapy and recovered within ≤ 7 days (with a shorter disease duration in children: ≤ 3 days in 29 (94%) cases). In 22 (31%) instances, the authors noted a link between the onset of meningitis and a rapid intravenous infusion of immunoglobulins. Cerebrospinal fluid analysis revealed a predominantly neutrophilic (N = 46, 66%) pleocytosis. Recurrences after re-exposure were observed in eight (N = 11%) patients. Eight case series addressed the prevalence of meningitis in 4089 patients treated with immunoglobulins. A pooled prevalence of 0.6% was noted. Finally, pharmacovigilance data revealed that meningitis temporally associated with intravenous immunoglobulin therapy occurred with at least five different products. In conclusion, intravenous immunoglobulin may cause an acute aseptic meningitis. The clinical features remit rapidly after discontinuing the medication.

RISK FACTORS OF VISION LOSS AND MULTIPLE RECURRENCES IN MYOPIC MACULAR NEOVASCULARIZATION.

PURPOSE: To investigate the factors associated with maximum visual improvement (peak vision) gain and the risk factors of peak vision loss and multiple recurrences in myopic macular neovascularization undergoing antivascular endothelial growth factor therapy. METHODS: Retrospective study of 310 eyes with active myopic macular neovascularization and median follow-up of 3.5 years. We defined peak vision gain as the maximum best-corrected visual acuity value reached under treatment and peak vision loss as best-corrected visual acuity never scoring as peak vision. We used multiple-event Prentice, Williams, and Peterson models to compute recurrences' incidence and Cox regression to identify risk factors for peak vision gain, peak vision loss, and multiple recurrences. RESULTS: Eyes with worse baseline best-corrected visual acuity {hazard ratio (HR) = 2.59 (95% confidence interval [CI]: 1.63-4.11) for 0.1 logMAR increase, P < 0.001} had higher chance to achieve peak vision. Peak vision was lost in 162 eyes (52%). Older age (HR = 1.22 [95% CI: 1.02-1.43] for 10-year increase, P = 0.02) and recurrences (HR = 1.10 [95% CI: 1.01-1.22] for event, P = 0.04) predicted nonsustained peak vision. Older age (HR = 1.13 [95% CI: 1.04-1.27] for 10-year increase, P = 0.006), larger myopic macular neovascularization (HR = 1.06 [95% CI: 1.01-1.13] for 1-mm 2 increase, P = 0.04), and juxtafoveal location (HR = 1.88 [95% CI: 1.28-2.77] vs. extrafoveal, P = 0.001) predicted multiple recurrences. CONCLUSION: Myopic macular neovascularization eyes lose vision mainly because of multiple recurrences. Patients at risk for recurrences should undergo more attentive monitoring to avoid vision loss.

Long-term Incidence and Risk Factors of Macular Fibrosis, Macular Atrophy, and Macular Hole in Eyes with Myopic Neovascularization.

PURPOSE: To identify the risk factors associated with myopic macular neovascularization (mMNV)-related complications in patients treated with intravitreal anti-VEGF agents. DESIGN: Longitudinal cohort study. PARTICIPANTS: Myopic eyes (n = 313) with active mMNV and median (interquartile range) follow-up of 42 months (interquartile range, 18-68 months) after initiation of anti-VEGF treatment. METHODS: Data regarding patients' clinical and mMNV-related characteristics were collected at baseline. Subsequent OCT scans were inspected for mMNV-related complications. Best-measured visual acuity (BMVA) values were retrieved from each visit. MAIN OUTCOME MEASURES: Incidence rate and hazard ratio (HR, with 95% confidence interval [CI]) of risk factors for fibrosis and macular atrophy calculated with Kaplan-Meier curves and Cox regression models. Crude incidence of macular hole (MH). Longitudinal BMVA changes. RESULTS: Five-year incidence of fibrosis, atrophy, and MH were 34%, 26%, and 8%, respectively. The rate of fibrosis was 10.3 (95% CI, 8.25-12.6) per 100 person-years. Risk factors were subfoveal mMNV location (HR [95% CI] = 12.7 [2.70-56.7] vs. extrafoveal, P = 0.001) and intraretinal fluid at baseline (HR [95% CI] = 1.75 [1.05-2.98], P = 0.03). The rate of macular atrophy was 6.5 (95% CI, 5-8.3) per 100 person-years. Risk factors were diffuse (HR, 2.20 vs. tessellated fundus; 95% CI, 1.13-5.45; P = 0.02) or patchy chorioretinal atrophy (HR, 3.17 vs. tessellated fundus; 95% CI, 1.32-7.64; P = 0.01) at baseline and more numerous anti-VEGF injections before baseline (HR, 1.21; 95% CI, 1.06-1.38 for each treatment; P = 0.005). Eyes with fibrosis and macular atrophy had faster BMVA decay over follow-up. Twenty eyes (6%) developed MH. Two subtypes of MH were identified: "atrophic" and "tractional." CONCLUSIONS: Myopic MNV-related complications are common in the long term despite initially successful treatment and have detrimental effects on visual acuity. Insights into their incidence and risk factors may help for future treatments to mitigate sight-threatening outcomes.