Subfoveal Choroidal Neovascular Membrane Secondary to Idiopathic Intracranial Hypertension.

Purpose: To present a rare case of subfoveal choroidal neovascular membrane (CNVM) secondary to idiopathic intracranial hypertension. Methods: A case was evaluated. Results: A 21-year-old woman presented with a 2-week history of painless blurred vision in the right eye. She described initial metamorphopsia and intermittent bitemporal headaches lasting 30 minutes. She denied pain with eye movements and a history of trauma. Her body mass index was 49 kg/m2. The visual acuity (VA) was 20/320 OD and 20/20 OS; there was no relative afferent pupillary defect. A dilated fundus examination showed bilateral optic disc edema and a subfoveal CNVM in the right eye. The patient was started on oral acetazolamide 500 mg twice daily and treated with 2 intravitreal antivascular endothelial growth factor (anti-VEGF) injections. Three months later, the VA was 20/30 in the right eye and the disc edema had improved. Conclusions: CNVMs in the setting of idiopathic intracranial hypertension-related papilledema may be subfoveal and have an excellent response to anti-VEGF agents.

Treat-and-extend dosing of intravitreal anti-VEGF agents in neovascular age-related macular degeneration: a meta-analysis.

Intravitreal injections of antiangiogenic agents are pivotal in treating neovascular age-related macular degeneration (nAMD). The comparative efficacy and safety of treat-and-extend (T&E) versus bimonthly, monthly, and pro re nata (PRN) dosing remains unclear. A systematic review and meta-analysis of English-language RCTs reporting on efficacy and/or safety outcomes of dosing regimens of anti-VEGF agents in nAMD was performed. Best-corrected visual acuity (BCVA, ETDRS letters) at last follow-up represented the primary endpoint, while central subfield thickness (CSFT, µm), injection burden, and ocular adverse events were secondary endpoints. A random effects meta-analysis was performed, and 95% confidence intervals were calculated. Across six RCTs, 781 T&E-, 663 monthly-, 130 PRN-, and 123 bimonthly treated eyes were included. Mean changes in BCVA and CSFT at last follow-up were similar between T&E versus monthly (WMD, -0.62 letters; 95% CI, -2.12 to 0.87; P = 0.41; WMD, 5.30 microns; 95% CI, -10.67 to 21.26; P = 0.52, respectively), bimonthly (WMD, 1.68 letters; 95% CI, -3.55 to 6.91; P = 0.53; WMD, -18.91 microns; 95% CI, -46.41 to 8.60; P = 0.18, respectively), and PRN (BCVA WMD, 1.08 letters; 95% CI, -2.95 to 5.11; P = 0.60) regimens. T&E was associated with a reduced injection burden versus monthly (WMD, -4.52 injections; 95% CI, -6.66 to 2.39; P < 0.001) but higher injection burden versus PRN (WMD, 1.81 injections; 95% CI, 1.12 to 2.51; P < 0.001) dosing. There was no significant difference in safety outcomes amongst comparators. There was no significant difference in efficacy and safety between T&E, bimonthly, monthly, and PRN dosing. T&E resulted in fewer injections versus monthly and fewer clinic visits versus PRN.

Safety and Efficacy of a Treat-and-Extend Regimen of Anti-Vascular Endothelial Growth Factor Agents for Diabetic Macular Edema or Macular Edema Secondary to Retinal Vein Occlusion: A Systematic Review and Meta-Analysis.

[Box: see text] Background and Objective: This meta-analysis evaluates treat-and-extend regimens relative to monthly and as-needed (prn) regimens using anti-vascular endothelial growth factor agents for diabetic macular edema and macular edema secondary to retinal vein occlusion. MATERIALS AND METHODS: Comparative studies evaluating a treat-and-extend regimen relative to a monthly or prn regimen with anti-vascular endothelial growth factor therapy for diabetic macular edema or macular edema secondary to retinal vein occlusion were included following a systematic literature search. RESULTS: Seven studies of 984 eyes were included. Relative to a monthly regimen, treat-and-extend was similar for change in best-corrected visual acuity at final follow-up (P = .59) and had a lower number of injections (P < .00001). Relative to a prn regimen, treat-and-extend was similar for change in best-corrected visual acuity at final follow-up (P = .84) and was associated with a higher number of injections (P = .02). CONCLUSION: This meta-analysis found that a treat-and extend regimen was nonsignificantly different compared to monthly and prn regimens in efficacy and safety end points. [Ophthalmic Surg Lasers Imaging Retina 2023;54(3):131-138.].

Investigating the role of inflammation in keratoconus: A retrospective analysis of 551 eyes.

PURPOSE: Keratoconus (KCN), classically defined as a noninflammatory corneal ectasia, was recently associated with chronic inflammation. This study aimed to further evaluate the association between inflammation and KCN severity by assessing patient tear films. METHODS: Retrospective chart review of consecutive patients (July 2016-February 2020) referred to a tertiary KCN centre. Using tomography Kmax values, the worst-eyes of patients with a diagnosis of KCN and tear film test results were included. Eyes were stratified as matrix metalloproteinase-9 (MMP9) positive or negative and analyzed using independent t and Pearson chi-squared tests. A p-value ≤ 0.05 was considered significant. RESULTS: 551 (51.40%) unilateral eyes were included. Mean age was 30.1 years and 70.1% were male. 55.5% of the eyes were MMP9 positive. Mean corrected distance visual acuity was 20/30<συπ>-3 Snellen and Kmax was 60.1 Diopters. MMP9 positive eyes had a higher Kmax (p = 0.048), and were more likely from patients who were male (p < 0.001), had a paediatric history of asthma (p = 0.042), and used glasses (p = 0.041). MMP9 negative eyes more likely corresponded to soft contact lens users (p = 0.012). No other significant differences were found in risk factors, topography, tomography, and tear film osmolarity. CONCLUSION: MMP9 positive keratoconic eyes had significantly higher Kmax readings which may correlate with increased disease severity, supporting an association between keratoconus and inflammation. Further research is warranted to evaluate the role of targeted therapy and contact lens use on MMP9 levels in keratoconic eyes and whether disease progression is affected.

Scleral Buckling Alone or in Combination with Pars Plana Vitrectomy for Rhegmatogenous Retinal Detachment Repair: A Meta-Analysis of 7,212 Eyes.

PURPOSE: The efficacy and safety of scleral buckling (SB) versus combination SB and pars plana vitrectomy (SB + PPV) for rhegmatogenous retinal detachment (RRD) repair remains unclear. METHODS: A systematic review and meta-analysis was conducted to identify comparative studies published from Jan 2000-Jun 2021 that reported on the efficacy and/or safety following SB and SB + PPV for RRD repair. Final best-corrected visual acuity (BCVA) represented the primary endpoint, while reattachment rates and ocular adverse events were secondary endpoints. A random-effects meta-analysis was performed, and 95% confidence intervals were calculated. RESULTS: Across 18 studies, 3912 SB and 3300 SB + PPV eyes were included. Final BCVA was nonsignificantly different between SB and SB + PPV (20/38 vs. 20/66 Snellen; WMD = -0.11 LogMAR; 95% CI: [-0.29, 0.07]; p = 0.23). Primary reattachment rate was similar between procedures (p = 0.74); however, SB alone achieved a significantly higher final reattachment rate (97.40% vs. 93.86%; RR = 1.03; 95% CI: [1.00, 1.06]; p = 0.04). Compared to SB + PPV, SB alone had a significantly lower risk of postoperative macular edema (RR = 0.69; 95% CI: [0.47, 1.00]; p = 0.05) and cataract formation (RR = 0.34; 95% CI: [0.12, 0.96]; p = 0.04). The incidence of macular hole, epiretinal membrane, residual subretinal fluid, proliferative vitreoretinopathy, elevated intraocular pressure, and extraocular muscle dysfunction were similar between SB and SB + PPV. CONCLUSIONS: There was no significant difference in final BCVA between SB + PPV and SB alone in RRD. SB alone offers a slightly higher final reattachment rate along with a reduced risk of macular edema and cataract. Primary reattachment rate and the incidence of other complications were similar between the two procedures.

Pars Plana Vitrectomy with and without Supplemental Scleral Buckle for the Repair of Rhegmatogenous Retinal Detachment: A Meta-analysis.

TOPIC: It is unclear whether there are differences in safety and efficacy between pars plana vitrectomy (PPV) alone and PPV with a supplemental scleral buckle (SB; PPV-SB) for the treatment of rhegmatogenous retinal detachment. CLINICAL RELEVANCE: This meta-analysis aimed to compare the safety and efficacy of these surgical procedures. METHODS: In this meta-analysis, Ovid MEDLINE, Embase, and Cochrane Library were systematically searched (January 2000-June 2021). The primary outcome was the final best corrected visual acuity (BCVA), whereas the secondary outcomes were reattachment rates and complications. The risk of bias was assessed using the Cochrane risk-of-bias tool for randomized controlled trials (RCTs) and the risk of bias in nonrandomized studies of interventions tool for nonrandomized studies. RESULTS: This study included 15 661 eyes from 38 studies (32 observational studies and 6 RCTs). The median follow-up duration was 6 months. The final BCVA was similar between PPV and PPV-SB (weighted mean difference [WMD], -0.03 logarithm of the minimum angle of resolution [-0.14 to 0.07]; P = 0.55). There was a significant difference in the single-operation success rate (SOSR) (88.2% versus 86.3%; relative risk [RR], 0.97 [0.95-1.00]; P = 0.03), favoring PPV-SB; however, there was no significant difference in the final reattachment rate (RR, 1.00 [0.99-1.01]; P = 0.56). Pars plana vitrectomy required a significantly higher number of operations to achieve final anatomical reattachment (WMD, 0.13 [0.02-0.24]; P = 0.02). In terms of complications, PPV was significantly less likely to be associated with macular edema (RR, 0.47 [0.25-0.88]; P = 0.02) and epiretinal membrane formation (RR, 0.70 [0.52-0.94]; P = 0.02), but these differences were no longer significant in studies published after 2010 or in RCTs. Significant proliferative vitreoretinopathy, lens status, and macular attachment status did not mediate differences in these effects. CONCLUSIONS: There were no significant differences in the final visual acuity outcomes between PPV and PPV-SB. Pars plana vitrectomy with supplemental SB was associated with a greater SOSR than standalone PPV, although the magnitude of the effect was small, with a high number needed to treat. The final reattachment rate was similar. In recent studies and in RCTs, the risk of complications was similar between the procedures.

Pars plana vitrectomy, scleral buckle, and pneumatic retinopexy for the management of rhegmatogenous retinal detachment: a meta-analysis.

We reviewed the literature on the efficacy and safety of pars plana vitrectomy (PPV), scleral buckle (SB), and pneumatic retinopexy (PR) for the management of rhegmatogenous retinal detachments (RRDs). A systematic search was performed on three databases from inception to September 2020. Randomized controlled trials (RCTs) comparing RRD management options were included. Meta-analysis was performed using a random effects model. Eighteen RCTs and 2,751 eyes were included. For PPV versus SB, early postoperative corrected distance visual acuity (CDVA) favored SB (weighted mean <1 month postoperatively: ~counting fingers for PPV versus ~20/260 for SB, P = 0.02), but differences were nonsignificant at other time points. There was no difference for primary reattachment (P = 0.08). PPV had a lower incidence of choroidal detachment (P = 0.004), hypotony (P = 0.01), and strabismus/diplopia (P = 0.04) but a higher incidence of iatrogenic breaks (P = 0.003) and cataract development/progression (P = 0.05) relative to SB. Combination management was nonsignificantly different relative to PPV alone for CDVA, complications and reattachment rate. In closing, PPV is associated with a slower visual recovery, but similar final visual acuity and primary reattachment rate relative to SB. Combination procedures did not improve primary reattachment rates or vision relative to standalone PPV. Heterogeneity was seen across the included trials, and further randomized trials are needed to reduce the uncertainty of these estimates.

Pars plana vitrectomy versus scleral buckle: A comprehensive meta-analysis of 15,947 eyes.

Pars plana vitrectomy (PPV) and scleral buckling (SB) are two of the most common surgical treatments for rhegmatogenous retinal detachment (RRD). This meta-analysis compares the efficacy and safety of PPV and SB for RRD. A systematic literature review was performed using Ovid MEDLINE, EMBASE and Cochrane CENTRAL from 2000 to June, 2021. Comparative studies, randomized controlled trials and observational studies investigating PPV and SB for RRD repair were included. The primary endpoint was final best- corrected visual acuity (BCVA). Secondary endpoints were reattachment rates, total operation time, and incidence of adverse events. Subgroup analyses including phakic status, presence of PVR-C or greater at baseline, and macular attachment status were conducted. Across 41 studies (8 RCTs, 33 observational studies), 5,401 SB and 10,546 PPV eyes were included. SB achieved a statistically significant, but likely not clinically significant, better final BCVA than PPV (0.38 ± 0.53 vs. 0.33 ± 0.53 logMAR (20/48 vs. 20/43 Snellen); weighted mean difference [WMD]: 0.07; 95% confidence interval: [0.02-0.11]; P = 0.005). SB had a better final BCVA compared to PPV in observational studies (P = 0.007) but not in RCTs (P = 0.21). SB had a lower incidence of post-operative cataract formation (P < 0.00001) and iatrogenic breaks (P < 0.00001), but a higher incidence of choroidal/subretinal hemorrhage (P = 0.007), choroidal detachment (P = 0.004), and residual subretinal fluid (RSRF) (P < 0.00001). Primary (86.5% vs. 84.8%; P = 0.13) and final (96.7% vs. 97.7%; P = 0.12) reattachment rates were similar between PPV and SB. PPV had a significantly higher primary reattachment rate in RCTs (P = 0.02) but not in observational studies (P = 0.30). SB was associated with a better final BCVA than PPV; however, this result was primarily driven by observational studies and phakic patients who developed cataracts. Primary and final reattachment rates were similar between the comparators. SB was associated with a significantly lower incidence of iatrogenic breaks and cataracts, while PPV was associated with a reduced risk of choroidal detachment, subretinal hemorrhage, and RSRF.

Frequency and source of prescription eyewear insurance coverage in Ontario: a repeated population-based cross-sectional study using survey data.

BACKGROUND: Insurance coverage may reduce cost barriers to obtain vision correction. Our aim was to determine the frequency and source of prescription eyewear insurance to understand how Canadians finance optical correction. METHODS: We conducted a repeated population-based cross-sectional study using 2003, 2005 and 2013-2014 Canadian Community Health Survey data from respondents aged 12 years or older from Ontario, Canada. In this group, the cost of prescription eyewear is not covered by the government unless one is registered with a social assistance program or belongs to a specific population. We determined the frequency and source of insurance coverage for prescription eyewear in proportions. We used survey weights provided by Statistics Canada in all analyses to account for sample selection, a complex survey, and adjustments for seasonal effect, poststratification, nonresponse and calibration. We compared unadjusted proportions and adjusted prevalence ratios (PRs) of having insurance. RESULTS: Insurance covered all or part of the costs of prescription eyewear for 62% of Ontarians in all 3 survey years. Of those insured, 84.1%-86.0% had employer-sponsored coverage, 9.0%-10.3% had government-sponsored coverage, and 5.7%-6.8% had private plans. Employer-sponsored coverage remained constant for those in households with postsecondary graduation but decreased significantly for those in households with less than secondary school graduation, from 67.0% (95% confidence interval [CI] 63.2%-70.8%) (n = 175 000) in 2005 to 54.6% (95% CI 50.1%-59.2%) (n = 123 500) in 2013-2014. Government-sponsored coverage increased significantly for those in households with less than secondary school graduation, from 29.2% (95% CI 25.5%-32.9%) (n = 76 400) in 2005 to 41.7% (95% CI 37.2%-46.1%) (n = 93 900) in 2013-2014. In 2013-2014, Ontarians in households with less than secondary school graduation were less likely than those with secondary school graduation to report employer-sponsored coverage (adjusted PR 0.79, 95% CI 0.75-0.84) but were more likely to have government-sponsored coverage (adjusted PR 1.27, 95% CI 1.06-1.53). INTERPRETATION: Sixty-two percent of Ontarians had prescription eyewear insurance in 2003, 2005 and 2013-2014; the largest source of insurance was employers, primarily covering those with higher education levels, whereas government-sponsored insurance increased significantly among those with lower education levels. Further research is needed to elucidate barriers to obtaining prescription eyewear and the degree to which affordability impairs access to vision correction.

Intravitreal antivascular endothelial growth factor injection versus laser photocoagulation for retinopathy of prematurity: A meta-analysis of 3,701 eyes.

We investigate the efficacy and safety of intravitreal injection (IVI) of antivascular endothelial growth factor agents and laser photocoagulation (LPC) for retinopathy of prematurity. We performed a systematic search of Ovid MEDLINE, EMBASE, and Cochrane CENTRAL (2005-2019). Comparative studies reporting on ocular efficacy and/or safety outcomes after IVIs and LPC for retinopathy of prematurity were included. The primary outcome was the regression rate, whereas secondary endpoints included the likelihood of requiring additional treatment, visual and refractive outcomes, and complications. Overall, 777 publications were identified. Twenty-four articles were included, with 1,289 eyes receiving IVI and 2,412 eyes undergoing LPC. There was no significant difference in the regression rate between IVI and LPC (P = 0.68); however, eyes that underwent IVI were associated with a significantly higher likelihood of requiring additional treatment (risk ratio = 2.16, 95% confidence interval (CI) = [1.26, 3.73], P = 0.005) and longer time from treatment to retreatment or recurrence (weighted mean difference = 6.43 weeks, 95% CI = [2.36, 10.51], P = 0.002). Eyes receiving IVI required surgical intervention significantly less often (risk ratio = 0.45, 95% CI = [0.23, 0.89], P = 0.02). Astigmatism was significantly lower after IVI relative to LPC (weighted mean difference = -0.25 D, 95% CI = [-0.45, -0.06], P = 0.01), and there was a lower proportion of emmetropic eyes at last follow-up after LPC (risk ratio = 0.51, 95% CI = [0.27, 0.99], P = 0.05). There were no differences in visual and safety outcomes between IVI and LPC. LPC had a lower likelihood of requiring additional treatment, whereas IVIs were associated with a longer interval from treatment to retreatment or recurrence, reduced risk of surgical intervention and superior refractive outcomes. All other outcomes were comparable between IVIs and LPC.

Microinvasive glaucoma surgery: A review of 3476 eyes.

Microinvasive glaucoma surgery (MIGS) is a potentially safer and more efficacious method studied in patients with mild-to-moderate open-angle glaucoma requiring less invasive treatment goals; however, the literature on MIGS must be thoroughly evaluated. We conducted a review of MIGS by searching MEDLINE, EMBASE, and Cochrane CENTRAL. Primary efficacy indicators were reductions in intraocular pressure and topical medication use postoperatively. While all comparative randomized controlled trials assessing MIGS in English peer-reviewed journals were included, only observational studies with a target follow-up of at least one year and a high priority score were analyzed, resulting in a total of 3476 eyes across 20 trials. The mean age was 69.5 ± 2.9 years, 53.7% were female, and 77.4% were Caucasian. One study had last follow-up at less than one year, fifteen studies had follow-up extending 1-2 years, and four had longer than two years of follow-up. A pattern of more significant intraocular pressure and medication reduction was observed in patients who underwent MIGS (n = 2170) relative to control (n = 1306) interventions. iStent had the most literature supporting its efficacy, followed by Hydrus. The most common adverse events after MIGS implantation included stent obstruction, inflammation, and subsequent surgical intervention. Surgical complication rates and efficacy are favorable after MIGS. This review helps to consolidate the high-quality evidence that exists for various MIGS procedures and to identify gaps where further research is needed.

Headache and Bilateral Optic Disc Edema as the Initial Manifestation of Vogt-Koyanagi-Harada Disease.

ABSTRACT: A 31-year-old healthy Asian man presented with new headaches and blurred vision. He was found to have bilateral optic disc edema (ODE) and peripapillary subretinal fluid and was initially investigated for causes of raised intracranial pressure. After referral to neuro-ophthalmology, he received a diagnosis of Vogt-Koyanagi-Harada (VKH) disease and his symptoms, ODE, and vision improved promptly with prednisone treatment. HLA typing was performed and returned positive for the HLA-DRB1*04 subtype. Although VKH disease usually presents with granulomatous uveitis or serous retinal detachments, ODE may manifest early in the disease course. Those with ODE in VKH disease are believed to be older and female, but this case demonstrates that these findings were also seen in a young man.

Retinal Manifestations of Idiopathic Intracranial Hypertension.

TOPIC: This review presents a case series and systematic review to understand retinal changes in patients with idiopathic intracranial hypertension (IIH) using fundus photography and OCT. CLINICAL RELEVANCE: IIH is a condition of raised intracranial pressure of unknown cause, usually observed in young, obese women. Ophthalmologic manifestations of IIH such as papilledema and abducens nerve palsy are well recognized, but less common retinal manifestations may occur. METHODS: A retrospective institutional chart review (July 2018-March 2020) was performed on consecutive IIH patients. Fundus photographs were obtained followed by neuro-ophthalmology assessment to elicit clinical characteristics and for diagnosis. Patients who met the modified Dandy criteria were included. A systematic review of observational studies was conducted using Ovid MEDLINE and EMBASE to November 17, 2019, to supplement the case series data. RESULTS: Of 144 consecutive IIH clinical patients reviewed, 10 (6.9%) and over 182 patients from the literature showed retinal findings (% in case series, % in literature, respectively): subretinal fluid (SRF; 30,9), chorioretinal folds (30,68), macular exudate (ME; 20,5), choroidal neovascular membrane (CNVM; 10,15), venous stasis retinopathy (VSR; 10,2), choroidal infarction (0,1), and branch retinal artery occlusion (BRAO; 0,1). Eight clinical patients were women (80%), average age was 32.00 ± 13.99 years, body mass index was 40.63 ± 7.43 kg/m2, baseline visual acuity (VA) was 0.79 ± 0.30 in both eyes, and visual field (VF) results were -9.89 ± 11.52 dB in both eyes. Among clinical patients, 2 (1 with SRF, 1 with CNVM) had distinctive retina-related VF defects at presentation. Outer retinal abnormalities persisted on OCT in patients after resolution of SRF and papilledema. Surgical treatment (peritoneal shunt) was required for 2 patients (1 with VSR, 1 with SRF); others were treated with weight loss and acetazolamide alone. The patient with significant ME had hypertension that was treated. DISCUSSION: Significant retinal manifestations associated with IIH include CNVM, ME, SRF, VSR, chorioretinal folds, choroidal infarction, and BRAO. These may reduce VA or cause VF defects unrelated to papilledema, emphasizing the importance of a detailed dilated fundus examination. Consultation with a retina specialist is advised in patients with peripapillary CNVM.

Vision Loss From Giant Cell Arteritis in Patients With Other Ocular Diagnoses.

ABSTRACT: Vision problems from giant cell arteritis (GCA) can be difficult to diagnose as patients may present with vision loss in the absence of systemic symptoms, have other comorbidities that affect inflammatory blood markers, or have other ocular diagnoses. We present 3 cases illustrating this point including a patient with advanced glaucoma with worsening vision from posterior ischemic optic neuropathy from GCA, a patient with arteritic anterior ischemic optic neuropathy (AAION) erroneously diagnosed as optic neuritis without elevated inflammatory blood markers due to corticosteroid use, and a patient with AAION and a history of nonarteritic anterior ischemic optic neuropathy in her fellow eye and untreated obstructive sleep apnea. GCA should be kept in the differential diagnosis for patients over 50 years of age even if they carry other ocular diagnoses. Temporal artery biopsy remains the gold standard for GCA diagnosis and is often required in equivocal cases.

Topical Nonsteroidal Anti-inflammatory Drugs for Pain Resulting from Intravitreal Injections: A Meta-Analysis.

TOPIC: The role of topical nonsteroidal anti-inflammatory drugs (NSAIDs) for the reduction of ocular pain after intravitreal injections (IVIs) has been explored. To provide clarity on the evidence for these agents, the present meta-analysis of randomized controlled trials (RCTs) was undertaken. CLINICAL RELEVANCE: No standard of care regimen exists for the management of pain resulting from IVIs. METHODS: A systematic literature search was conducted on Ovid MEDLINE, EMBASE, and Cochrane Central from inception through July 2019. The RCTs that treated patients with a topical NSAID and assessed postprocedural pain were included. Risk of bias was assessed using the Cochrane guidelines. For all analyses, weighted mean differences (WMDs) with 95% confidence intervals (CIs) were reported. Random effects models were used for all analyses. The primary analysis analyzed pain on a 0- to 10-point visual analog scale. Literature estimates were categorized into the following postprocedure time point groups: 1 hour or less, 1 to 24 hours (although data were available only at 6 hours), and 24 hours or more. A subgroup analysis stratified studies based on agent and preprocedure versus postprocedure administration. RESULTS: From 241 results, 9 RCTs and 598 eyes were included. A low to medium risk of bias was found across the included studies. The mean pain score on a 0-to-10 visual analog scale was significantly lower after topical NSAID administration relative to control at 1 hour or less after IVI (WMD, -1.01 units; 95% CI, -1.38 to -0.65; P < 0.001), 6 hours after IVI (WMD, -2.17 units; 95% CI, -2.67 to -1.68; P < 0.001; threshold met for clinical significance, defined as WMD >1.2 units), and more than 24 hours after IVI (WMD, -0.75 units; 95% CI, -1.11 to -0.38; P < 0.001). A greater effect size was seen with administration of NSAIDs before versus after IVI, as well as topical nepafenac relative to ketorolac or diclofenac. DISCUSSION: At 6 hours after the procedure, NSAIDs provide a clinically meaningful reduction in pain relative to a control group. The administration of NSAIDs before the procedure, specifically topical nepafenac, was associated with the greatest improvement in pain relative to the control group.