Long-Term Follow-Up before and during Riluzole Treatment in Six Patients from Two Families with Spinocerebellar Ataxia Type 7.

BACKGROUND: Currently no curative treatment exists for spinocerebellar ataxias (SCAs). Riluzole repurposing was proposed as a symptomatic treatment in different types of cerebellar ataxia. We report a long-term-follow up under riluzole treatment in SCA type 7. METHODS: Six patients received Riluzole 50 mg twice daily on a compassionate use program for a mean of 4.8 years (range 3.5-9). We measured ataxia onset and progression through the Scale for the Assessment and Rating of Ataxia (SARA), and collected extensive ophthalmological data before and after Riluzole treatment. Electrocardiogram and laboratory profile for drug safety were performed every six months. RESULTS: Riluzole treatment showed no effect on visual function in two patients with an advanced retinal damage. Improvements of visual function occurred in four patients followed by ophthalmologic stability up to 5 years after starting treatment. Two patients had a less steep deterioration of ataxia after treatment compared to pre-treatment, during the first 2,5 years of therapy. One showed soon after therapy an improvement of the SARA score, and then overall stability lasting 3,5 years, followed by ataxia worsening. One visually impaired patient without neurological impairment did not worse until the last visit after 3,5 years of follow-up. The remaining 2 patients showed an improvement of SARA scores soon after therapy, and an overall stability lasting respectively 5 and 3 years. No adverse event was registered during the observation period. DISCUSSION: This study suggests a possible beneficial action of Riluzole in SCA7 and provides a detailed description of the ophthalmologic profile of these patients.

Pre-stimulus bioelectrical activity in light-adapted ERG under blue versus white background.

To compare the baseline signal between two conditions used to generate the photopic negative response (PhNR) of the full-field electroretinogram (ERG): red flash on a blue background (RoB) and white flash on a white background (LA3). The secondary purpose is to identify how the level of pre-stimulus signal affects obtaining an unambiguous PhNR component. A retrospective chart review was conducted on four cohorts of patients undergoing routine ERG testing. In each group, LA3 was recorded the same way while RoB was generated differently using various luminances of red and blue light. The background bioelectrical activity 30 ms before the flash was extracted, and the root mean square (RMS) of the signal was calculated and compared between RoB and LA3 using Wilcoxon test. Pre-stimulus noise was significantly higher under RoB stimulation versus LA3 in all four conditions for both right and left eyes (ratio RoB/LA3 RMS 1.70 and 1.57 respectively, p < 0.033). There was also no significant difference between the RMS of either LA3 or RoB across protocols, indicating that the baseline noise across cohorts were comparable. Additionally, pre-stimulus noise was higher in signals where PhNR was not clearly identifiable as an ERG component versus signals with the presence of unambiguous PhNR component under RoB in all four groups for both eyes (p < 0.05), whereas the difference under LA3 was less pronounced. Our study suggests that LA3 produces less background bioelectrical activity, likely due to decreased facial muscle activity. As it seems that the pre-stimulus signal level affects PhNR recordability, LA3 may also produce a better-quality signal compared to RoB. Therefore, until conditions for a comparable bioelectrical activity under RoB are established, we believe that LA3 should be considered at least as a supplementary method to evaluate retinal ganglion cell function by ERG.

Effect of spatial averaging on the amplitude ring ratio in multifocal electroretinography.

PURPOSE: The purpose of this study was to evaluate the effect of spatial averaging on the multifocal electroretinography (mfERG) amplitude ring ratios used in screening for hydroxychloroquine (HCQ) toxicity. METHODS: This was a retrospective review of the records of patients screened for HCQ retinopathy at the USF Eye Institute (University of South Florida) during the period of 2015-2020. Patients were tested binocularly with Diagnosys mfERG system (Diagnosys LLC, Lowell, MA). Only the records of patients referred internally were used. The effects of the lowest level (level 1, or 8%) of spatial averaging on the P1 amplitude ring ratios used for screening of HCQ maculopathy: R1/R2, R2/R5, R5/R3 and R5/R4, were evaluated. RESULTS: The records of 40 patients (4 males, 36 females) aged 54.4 ± 14.1 years were selected for analysis. The use of spatial averaging had a significant effect on P1 amplitudes, and on the ring ratios and this effect was correlated with the magnitude of the amplitudes and the ratios. Spatial averaging diminished P1 amplitude significantly in ring 1 (p < 0.0001) and increased it slightly in ring 4 (p < 0.05), while it had no effect on the amplitude of the other three rings. Although as a group spatial averaging had a moderate effect on the R1/R2 ratio (~ -15%), on an individual basis the range was wide, from -36 to 43%. The effect on the other ring ratios was similar: The average group effect was ~ -5%, ~ -3.4% and ~ -4% for R2/R5, R5/R3 and R5/R4 ratios, but individual effects ranged from 0.18% to -27.3%, 0.9% to -14.2% and 0.9% to -26.2%, respectively. CONCLUSIONS: For all ring ratios used in this analysis, spatial averaging has a substantial effect on the ring ratio, which could affect the interpretation of the results. Therefore, use of spatial averaging should be avoided when analyzing mfERG results for HCQ screening.

Relationship between stimulus size and different components of the electroretinogram (ERG) elicited by flashed stimuli.

PURPOSE: To investigate how light stimulus conditions of varying spatial sizes affect components of the flash and long-flash electroretinogram (ERG) in normal subjects. METHOD: Three stimulus conditions were generated by a Ganzfeld stimulator: a white flash on white background (WoW), a red flash on a blue background (RoB) and an L+M-cone isolating on-off (long flash) stimulus (Cone Iso). ERGs were recorded from six subjects (5 M, 1 F) with DTL electrodes to full-field (FF), 70°, 60°, 50°, 40°, 30° and 20° diameter circular stimuli. Amplitudes and peak times for a-, b-, d- and i-wave, and PhNR were examined. PhNR amplitudes were estimated in two different ways: from baseline (fB) and from preceding b-wave peak (fP). RESULTS: With decreasing stimulus size, amplitudes for all ERG waveform components attenuated and peak times increased, although the effect varied across different components. An exponential fit described the relationship between amplitudes and size of stimulated retinal area well for most components and conditions (R2= 0.75-0.99), except for PhNR(fB) (R2= - 0.16-0.88). For peak times, an exponential decay function also fitted the data well (R2= 0.81-0.97), except in a few cases where the exponential constant was too small and a linear regression function was applied instead (a-wave Cone Iso, b- and i-wave WoW). The exponential constants for RoB amplitudes (b-wave, PhNR(fB), PhNR(fP)) were larger compared to their counterparts under WoW (p < 0.05), while there was no difference between the constants for a-wave amplitudes and peak times and for PhNR peak times. The exponential constants of amplitudes vs. area under WoW and Cone Iso were remarkably similar, while under RoB PhNR(fB) showed larger constants compared to either a- or b-wave (p < 0.05). CONCLUSION: ERG components change in a predictable way with stimulus size and spectral characteristics of the stimulus under these conditions. This predictability could allow a modified version of these sets of stimuli to be tested for clinical applicability.

A New Two-Step Anesthesia for 23- or 25-Gauge Vitrectomy Surgery: A Prospective, Randomized Clinical Trial.

OBJECTIVE: To investigate the safety and efficacy of topical anesthesia combined with subconjunctival anesthesia (termed two-step anesthesia) for 23- or 25-gauge pars plana vitrectomy or other posterior segment surgery. METHODS: Patients (n = 90) requiring 23-/25-gauge vitrectomy or other posterior segment surgery were randomized into 3 groups. Group 1 received peribulbar anesthesia, group 2 received retrobulbar anesthesia and group 3 received two-step anesthesia. A 5-point visual analog pain scale (VAPS) was used to measure self-report of patient pain. Complications were recorded for subsequent analysis. RESULTS: VAPS scores for overall intraoperative pain ranged from 0 to 3 (1.07 ± 1.07) in group 1, from 0 to 2 (0.69 ± 0.93) in group 2 and from 0 to 3 (1.06 ± 0.98) in group 3. Assessment of surgeon discomfort score ranged from 0 to 2 (0.31 ± 0.66) in group 1, from 0 to 3 (0.38 ± 0.82) in group 2 and from 0 to 2 (0.47 ± 0.62) in group 3. Both scores reveal no significant difference among the 3 groups. While there were no complications noted in group 1, there was an ocular perforation in group 2. Additionally, there were no complications in group 3 related to the anesthetic technique. CONCLUSIONS: Results suggest that two-step anesthesia is a safe and effective anesthetic approach for selected patients undergoing 23- or 25-gauge pars plana vitrectomy or other posterior segment surgeries. It may offer a viable alternative to peribulbar anesthesia and retrobulbar anesthesia for carefully selected 23- or 25-gauge cannular-access ocular surgeries.

ISCEV extended protocol for derivation and analysis of the strong flash rod-isolated ERG a-wave.

The International Society for the Clinical Electrophysiology of Vision (ISCEV) standard for full-field electroretinography (ERG) describes a minimum set of tests, but encourages the use of additional protocols for clinical ERG testing. This extended protocol describes recording methods and derivations that will allow analysis of rod-driven components of the dark-adapted (DA) strong flash ERG a-wave, more closely related to rod phototransduction than ISCEV standard DA ERGs. The method involves recording ERGs to a flash strength equivalent to 30 cd s m2 under conditions of dark adaptation and additionally to the same stimulus following light adaptation (LA) and in the presence of a standard photopic background luminance of 30 cd m-2. The isolated rod-driven ERG a-wave is derived by subtracting the LA response from the DA ERG. The method is likely to be of value in the characterization of retinal disorders which affect rod quantal catch, diseases that affect the dynamics of any component of the activation phase of rod phototransduction, or those affecting total numbers of rod photoreceptors.

The photopic negative response of the Light-adapted 3.0 ERG in clinical settings.

PURPOSE: To analyze the effects of different methods of measurement on the photopic negative response (PhNR), recorded as part of a standard ISCEV Photopic 3.0 ERG responses from patients with a variety of clinical diagnoses. METHODS: ERGs were recorded from both eyes of 97 patients (187 eyes) as part of a standard clinical assessment. The average age was 56.4 ± 15.7 years, the gender balance was 35 M, 62F, and only recordable responses of acceptable quality were included. PhNR was measured at an identifiable trough before (PhNR1) and after the i-wave (PhNR2), and the amplitudes and peak times were compared with a-, b- and i-wave corresponding parameters. PhNR components were measured: from baseline and from b-wave peak. Correlation between PhNR troughs and with ERG parameters were tested for right eyes. The possibility to predict and substitute PhNR2 amplitude from PhNR1 amplitude was also tested. RESULTS: PhNR1 was recordable in 97.3% of eyes and PhNR2 in 85.6%. An identifiable PhNR2 peak was found to occur before 65 ms at ~ 50% of the records, while in ~ 38% of the cases was within 65-75 ms in ~ 12%-after 75 ms. The correlation between the PhNR1 and PhNR2 peaks was quite strong (with coefficients 0.81-0.98, depending on method of measurement, and slopes close to 1). The average difference between predicted and measured PhNR2 was reasonably small in absolute (< 2 µV) and relative (< 2%) terms. The correlations between PhNR amplitudes and other ERG component amplitudes showed different ranges of correlation coefficients depending on the method of measurement: for the a-wave amplitudes the range of coefficients was 0.48-0.73, while for the b-wave amplitudes it was 0.30-0.95 and 0.39-0.65 for i-wave. CONCLUSION: The strong correlation between the two PhNR troughs could allow using PhNR1 when PhNR2 is poorly defined due to artifacts. Different methods of PhNR measurement lead to different correlations with other ERG parameters, and this needs to be considered when analyzing and comparing PhNR data between studies.

CCL20-CCR6 axis modulated traumatic brain injury-induced visual pathologies.

BACKGROUND: Traumatic brain injury (TBI) is a major cause of death and disability in the USA and the world; it constitutes 30% of injury-related deaths (Taylor et al., MMWR Surveill Summ 66:1-16, 2017). Contact sports athletes often experience repetitive TBI (rTBI), which exerts a cumulative effect later in life. Visual impairment is a common after-effect of TBI. Previously, we have shown that C-C chemokine 20 (CCL20) plays a critical role in neurodegeneration and inflammation following TBI (Das et al., J Neuroinflammation 8:148, 2011). C-C chemokine receptor 6 (CCR6) is the only receptor that CCL20 interacts with. The objective of the present study was to investigate the role of CCL20-CCR6 axis in mediating rTBI-induced visual dysfunction (TVD). METHODS: Wild type (WT) or CCR6 knock out (CCR6-/-) mice were subjected to closed head rTBI. Pioglitazone (PG) is a peroxisome proliferator-activated receptor γ (PPARγ) agonist which downregulates CCL20 production. Subsets of WT mice were treated with PG following final rTBI. A subset of mice was also treated with anti-CCL20 antibody to neutralize the CCL20 produced after rTBI. Histopathological assessments were performed to show cerebral pathologies, retinal pathologies, and inflammatory changes induced by rTBI. RESULTS: rTBI induced cerebral neurodegeneration, retinal degeneration, microgliosis, astrogliosis, and CCL20 expression. CCR6-/- mice showed reduced retinal degeneration, microgliosis, and inflammation. Treatment with CCL20 neutralization antibody or PG showed reduced CCL20 expression along with reduced retinal degeneration and inflammation. rTBI-induced GFAP-positive glial activation in the optic nerve was not affected by knocking out CCR6. CONCLUSION: The present data indicate that rTBI-induced retinal pathology is mediated at least in part by CCL20 in a CCR6-dependent manner.

INCIDENCE OF ENDOPHTHALMITIS AFTER VITRECTOMY: A Systematic Review and Meta-analysis.

PURPOSE: The purpose of this study was to review the literature reporting rates of postoperative endophthalmitis after pars plana vitrectomy and investigate whether modern microincision vitrectomy surgery (MIVS) increases the postoperative endophthalmitis rate, compared with traditional 20-gauge (20 G) vitrectomy. METHODS: A comprehensive literature search was performed to identify studies describing the incidence of post-pars plana vitrectomy endophthalmitis. A meta-analysis of comparative studies reporting the endophthalmitis rates after MIVS versus 20 G vitrectomy was also conducted. RESULTS: A total of 31 studies reported 199 endophthalmitis cases in 363,544 participants (0.05%). The incidence of endophthalmitis after 20 G vitrectomy was 0.04% (88/229,435), compared with 0.03% (8/27,326) after 23 G and 0.11% (33/29,676) after 25 G. The meta-analysis demonstrated that the incidence of endophthalmitis was higher after MIVS (23 G/25 G) compared with 20 G vitrectomy (odds ratio = 3.39, 95% confidence interval, 1.39-8.23). In a subgroup analysis, we also found an increased risk of endophthalmitis after 25 G compared with 20 G vitrectomy (odds ratio = 4.09, 95% confidence interval, 2.33-7.18), but not for 23 G versus 20 G (odds ratio = 1.14, 95% confidence interval, 0.47-2.78). CONCLUSION: The incidence of post-pars plana vitrectomy endophthalmitis was low, with no significant differences between 23 G MIVS and 20 G vitrectomy, but 25 G MIVS may result in a higher postoperative endophthalmitis rate.

ISCEV extended protocol for the photopic negative response (PhNR) of the full-field electroretinogram.

The International Society for Clinical Electrophysiology of Vision (ISCEV) Standard for full-field electroretinography (ERG) describes a minimum procedure, but encourages more extensive testing. This ISCEV extended protocol describes an extension to the ERG Standard, namely the photopic negative response (PhNR) of the light-adapted flash ERG, as a well-established technique that is broadly accepted by experts in the field. The PhNR is a slow negative-going wave after the b-wave that provides information about the function of retinal ganglion cells and their axons. The PhNR can be reduced in disorders that affect the innermost retina, including glaucoma and other forms of optic neuropathy. This document, based on existing literature, provides a protocol for recording and analyzing the PhNR in response to a brief flash. The protocol includes full-field stimulation, a frequency bandwidth of the recording in which the lower limit does not exceed 0.3 Hz, and a spectrally narrowband stimulus, specifically, a red flash on a rod saturating blue background. Suggested flash strengths cover a range up to and including the minimum required to elicit a maximum amplitude PhNR. This extended protocol for recording the PhNR provides a simple test of generalized retinal ganglion cell function that could be added to standard ERG testing.

Efferent influences on the bioelectrical activity of the retina in primates.

PURPOSE: The existence of retinopetal (sometimes referred to as "efferent" or "centrifugal") axons in the mammalian optic nerve is a topic of long-standing debate. Opposition is fading as efferent innervation of the retina has now been widely documented in rodents and other animals. The existence and function of an efferent system in humans and non-human primates has not, though, been definitively established. Such a feedback pathway could have important functional, clinical, and experimental significance to the field of vision science and ophthalmology. METHODS: Following a comprehensive literature review (PubMed and Google Scholar, until July 2016), we present evidence regarding a system that can influence the bioelectrical activity of the retina in primates. RESULTS: Anatomical and physiological evidences are presented separately. Improvements in histological staining and the advent of retrograde nerve fiber tracers have allowed for more confidence in the identification of efferent optic nerve fibers, including back to their point of origin. CONCLUSION: Even with the accumulation of more modern anatomical and physiological evidence, some limitations and uncertainties about crucial details regarding the origins and role of a top-down, efferent system still exist. However, the summary of the evidence from earlier and more modern studies makes a compelling case in support of such a system in humans and non-human primates.

Inhibition or Stimulation of Autophagy Affects Early Formation of Lipofuscin-Like Autofluorescence in the Retinal Pigment Epithelium Cell.

The accumulation of lipofuscin in the retinal pigment epithelium (RPE) is dependent on the effectiveness of photoreceptor outer segment material degradation. This study explored the role of autophagy in the fate of RPE lipofuscin degradation. After seven days of feeding with either native or modified rod outer segments, ARPE-19 cells were treated with enhancers or inhibitors of autophagy and the autofluorescence was detected by fluorescence-activated cell sorting. Supplementation with different types of rod outer segments increased lipofuscin-like autofluorescence (LLAF) after the inhibition of autophagy, while the induction of autophagy (e.g., application of rapamycin) decreased LLAF. The effects of autophagy induction were further confirmed by Western blotting, which showed the conversion of LC3-I to LC3-II, and by immunofluorescence microscopy, which detected the lysosomal activity of the autophagy inducers. We also monitored LLAF after the application of several autophagy inhibitors by RNA-interference and confocal microscopy. The results showed that, in general, the inhibition of the autophagy-related proteins resulted in an increase in LLAF when cells were fed with rod outer segments, which further confirms the effect of autophagy in the fate of RPE lipofuscin degradation. These results emphasize the complex role of autophagy in modulating RPE autofluorescence and confirm the possibility of the pharmacological clearance of RPE lipofuscin by small molecules.

Retinal cross talk in the mammalian visual system.

The existence and functional relevance of efferent optic nerve fibers in mammals have long been debated. While anatomical evidence for cortico-retinal and retino-retinal projections is substantial, physiological evidence is lacking, as efferent fibers are few in number and are severed in studies of excised retinal tissue. Here we show that interocular connections contribute to retinal bioelectrical activity in adult mammals. Full-field flash electroretinograms (ERGs) were recorded from one or both eyes of Brown-Norway rats under dark-adapted (n = 16) and light-adapted (n = 11) conditions. Flashes were confined to each eye by an opaque tube that blocked stray light. Monocular flashes evoked a small (5-15 µV) signal in the nonilluminated eye, which was named "crossed ERG" (xERG). The xERG began under dark-adapted conditions with a positive (xP1) wave that peaked at 70-90 ms and ended with slower negative (xN1) and positive (xP2) waves from 200 to 400 ms. xN1 was absent under light-adapted conditions. Injection of tetrodotoxin in either eye (n = 15) eliminated the xERG. Intraocular pressure elevation of the illuminated eye (n = 6) had the same effect. The treatments also altered the ERG b-wave in both eyes, and the alterations correlated with xERG disappearance. Optic nerve stimulation (n = 3) elicited a biphasic compound action potential in the nonstimulated nerve with 10- to 13-ms latency, implying that the xERG comes from slow-conducting (W type) fibers. Monocular dye application (n = 7) confirmed the presence of retino-retinal ganglion cells in adult rats. We conclude that mammalian eyes communicate directly with each other via a handful of optic nerve fibers. The cross talk alters retinal activity in rats, and perhaps other animals.

SUBTHRESHOLD MICROPULSE DIODE LASER VERSUS CONVENTIONAL LASER PHOTOCOAGULATION FOR DIABETIC MACULAR EDEMA: A Meta-Analysis of Randomized Controlled Trials.

PURPOSE: To evaluate the relative efficacy of subthreshold micropulse diode laser versus conventional laser photocoagulation for the treatment of diabetic macular edema. METHODS: A comprehensive literature search was conducted to find relevant randomized controlled trials (RCTs). Efficacy estimates were determined by comparing weighted mean differences of the mean change of best-corrected visual acuity and central macular thickness from baseline. RESULTS: Six RCTs were selected for this meta-analysis, including 398 eyes (203 eyes in the subthreshold micropulse diode laser group and 195 eyes in the conventional laser group). Subthreshold micropulse diode laser was superior to conventional laser in terms of mean change of logMAR best-corrected visual acuity at 3, 9, and 12 months after treatment (P = 0.02; P = 0.04, and P = 0.03, respectively), and it showed a similar trend at 6 months (P = 0.05). Although, there was no significant difference in terms of mean change in central macular thickness from baseline to 3, 6, 9, or 12 months (P = 0.80; P = 0.20; P = 0.88, and P = 0.86, respectively). CONCLUSION: Subthreshold micropulse diode laser treatment resulted in better visual acuity compared with conventional laser, although the differences before 12 months are likely to be too small to be of clinical relevance and may be dependent on baseline best-corrected visual acuity. The two types of treatment seem to have similar anatomical outcome.

Inflammatory changes in optic nerve after closed-head repeated traumatic brain injury: Preliminary study.

BACKGROUND: Closed-head, repeated, mild traumatic brain injury (r-mTBI) leads to inflammatory and degenerative changes in the optic nerve of young wild type mice. This work has investigated whether similar changes may be present when the same model is applied to htau mice, a transgenic mouse in which the non-mutated human tau gene is expressed on a null murine tau background. METHODS: This study investigated neuropathological changes in the optic nerve in both young (15 weeks) and old (65-70 weeks) htau mice at 24 hours after r-mTBI or anaesthesia only (r-sham). Change in the level of cellularity, myelin content and astroglial reactivity were evaluated in optic nerve samples. RESULTS: Increased cellularity and areas of demyelination were clearly detectable in the intracranial portion of the optic nerve in both young (10-15 weeks) and old (65-75) htau r-mTBI mice at 24 hours post-injury, in contrast to r-sham. Increased astroglial reactivity was also observed, together with increased tau phosphorylation. CONCLUSIONS: Localized inflammatory and degenerative response of the intracranial part of the optic nerve was detected in htau mice after r-mTBI. Further studies to clarify the cause and consequences of this phenomenon are warranted.

ISCEV Standard for full-field clinical electroretinography (2015 update).

This document, from the International Society for Clinical Electrophysiology of Vision (ISCEV), presents an updated and revised ISCEV Standard for full-field clinical electroretinography (ffERG or simply ERG). The parameters for Standard flash stimuli have been revised to accommodate a variety of light sources including gas discharge lamps and light emitting diodes. This ISCEV Standard for clinical ERGs specifies six responses based on the adaptation state of the eye and the flash strength: (1) Dark-adapted 0.01 ERG (rod ERG); (2) Dark-adapted 3 ERG (combined rod-cone standard flash ERG); (3) Dark-adapted 3 oscillatory potentials; (4) Dark-adapted 10 ERG (strong flash ERG); (5) Light-adapted 3 ERG (standard flash "cone" ERG); and (6) Light-adapted 30 Hz flicker ERG. ISCEV encourages the use of additional ERG protocols for testing beyond this minimum standard for clinical ERGs.

Bevacizumab versus ranibizumab for neovascular age-related macular degeneration: a meta-analysis of randomized controlled trials.

PURPOSE: To evaluate the relative efficacy and safety of bevacizumab versus ranibizumab for the treatment of the neovascular form of age-related macular degeneration. METHODS: A comprehensive literature search using the Cochrane Methodology Register to identify randomized controlled trials comparing bevacizumab with ranibizumab in patients with neovascular age-related macular degeneration. Efficacy estimates were determined by comparing weighted mean differences in the change of best-corrected visual acuity and central macular thickness from baseline. Safety estimates were determined by calculating the risk ratio for rates of death, arteriothrombotic events, venous thrombotic events, and at least 1 serious systemic adverse event. Statistical analysis was performed using the RevMan 5.1 software. RESULTS: A total of 6 randomized controlled trials were selected for this meta-analysis, including 2,612 patients (1,292 patients in the bevacizumab group and 1,320 patients in the ranibizumab group). There were no significant differences between bevacizumab and ranibizumab in best-corrected visual acuity mean change at 1 year or 2 years (weighted mean difference = -0.40, 95% confidence interval [CI], -1.48 to 0.69, P = 0.47 and weighted mean difference = -1.16, 95% CI, -2.82 to 0.51, P = 0.17, respectively). Ranibizumab was found to be more efficacious in reducing central macular thickness at 1 year (weighted mean difference = 4.35, 95% CI, 0.92-7.78, P = 0.01). The pooled risk ratios comparing the rates of serious systemic adverse events at 1 year and 2 years were slightly in favor of ranibizumab (risk ratio = 1.24, 95% CI, 1.04-1.48, P = 0.02 and risk ratio = 1.20, 95% CI, 1.05-1.37, P = 0.008, respectively), whereas the rates of death, arteriothrombotic events, and venous thrombotic events did not differ statistically. CONCLUSION: Bevacizumab and ranibizumab had equivalent efficacy for best-corrected visual acuity in the treatment of neovascular age-related macular degeneration. Ranibizumab tended to have a better anatomical outcome. There were no differences between drugs in rates of death, arteriothrombotic events or venous thrombotic events, and differences in rates of serious systemic adverse events that require further study.