The 50 most-cited articles in American Journal of Ophthalmology, 2024

PURPOSE: To discuss the clinical trial results leading to the US Food and Drug Administration (FDA) approval of anti-complement therapies for geographic atrophy (GA), perspectives on functional data from the GA clinical trials, and how lessons from the FDA approval may guide future directions for basic and clinical research in AMD. DESIGN: Selected literature review with analysis and perspective METHODS: We performed a targeted review of publicly available data from the clinical trials of pegcetacoplan and avacincaptad for the treatment of GA, as well as scientific literature on the natural history of GA and the genetics and basic science of complement in AMD. RESULTS: The approval of pegcetacoplan and avacincaptad was based on an anatomic endpoint of a reduction in the rate of GA expansion over time. However, functional data from 2 phase 3 clinical trials for each drug demonstrated no visual benefit to patients in the treatment groups. Review of the genetics of AMD and the basic science of the role for complement in AMD provides only modest support for targeting complement as…

PURPOSE: To assess the safety and efficacy of AAV5-hRKp.RPGR in participants with retinitis pigmentosa GTPase regulator (RPGR)-associated X-linked retinitis pigmentosa (XLRP). DESIGN: Open-label, phase 1/2 dose escalation/expansion study (ClinicalTrials.gov Identifier: NCT03252847). METHODS: vg/ml) was administered to the poorer-seeing eye (n = 10). Dose confirmation (intermediate dose) was carried out in 3 pediatric participants. In the dose expansion phase, 36 participants were randomized 1:1:1 to immediate (low or intermediate dose) or deferred (control) treatment. The primary outcome was safety. Secondary efficacy outcomes included static perimetry, microperimetry, vision-guided mobility, best corrected visual acuity, and contrast sensitivity. Safety and efficacy outcomes were assessed for 52 weeks for immediate treatment participants and 26 weeks for control participants. RESULTS: AAV5-hRKp.RPGR was safe and well tolerated, with no reported dose-limiting events. Most adverse events (AEs) were transient and related to the surgical procedure, resolving without intervention. Two…

PURPOSE: To evaluate the effectiveness and safety of repeated low-level red-light (RLRL) in delaying the progression of high myopes with -6.00 diopters (D) or worse. DESIGN: Multicenter, randomized, parallel-group, single-blind clinical trial. A total of 202 high myopic children aged 7 to 12 years with cycloplegia spherical equivalent (SE) refraction ≤-6.00 D, astigmatism less than 2.50 D, and anisometropia of 1.50 D or less were enrolled from March 2022 to December 2022. Follow-up was completed in December 2023. METHODS: Eligible participants were randomly allocated to the intervention (RLRL + single vision spectacle) or the control group (single vision spectacle). The RLRL treatment was administered every day for 3 minutes, twice a day, with an interval of at least 4 hours. The primary outcome was the change in axial length (AL) at 12 months compared with baseline. Secondary outcomes included changes in SE, changes in choroidal thickness (ChT), and changes in retinal thickness (RT) in different circle sectors. Outcomes were analyzed by means of intention-to-treat and per-protocol…

PURPOSE: Spectacle lenses with highly aspherical lenslets (HAL) have been shown to effectively retard myopia progression in myopic children. This study aimed to investigate the impact of spectacle lenses with HAL on refractive and axial length (AL) changes in Chinese children with low amount of hyperopia. DESIGN: Randomized controlled trial. METHODS: A total of 108 Chinese children aged 6.0 to 9.9 years and spherical equivalent refractive error (SERE) from 0.00 to +2.00 D were randomly allocated into two groups: the HAL group and the single vision spectacle lens (SVL) group. Cycloplegic refraction, AL, and uncorrected visual acuity were measured at baseline, 6 and 12 months after lens dispensing. The duration of spectacle lens wear was monitored using a wearable device attached to the spectacle frame and by questionnaire logs provided by participants at each follow-up visit. RESULTS: The 1-year SERE change was -0.19 (-0.32, 0.03) D and -0.23 (-0.36, 0.05) D in the SVL and HAL groups (P = .883). The 1-year AL elongation was 0.24 (0.18, 0.34) mm and 0.19 (0.12, 0.27) mm in the SVL and…

PURPOSE: To describe the patient characteristics and clinical course of severe intraocular inflammation (IOI) following intravitreal injection (IVT) of faricimab. DESIGN: Retrospective case series. METHODS: Case series at a single French academic center (Dijon University Hospital) where 263 patients were treated with faricimab IVT between January 9, 2024 and May 7, 2024. RESULTS: Over the 4-month period, a total of 1659 eyes (1338 patients) received anti-vascular endothelial growth factor (anti-VEGF) IVTs for a total of 3510 IVTs, of which 343 eyes (263 patients) received faricimab IVTs for a total of 971 IVTs. Overall, 6 pretreated eyes with neovascular age-related macular degeneration that were switched to faricimab developed severe unilateral IOI following faricimab IVT (1/162 injections [0.62%]), including 5 eyes presenting with a severe anterior and intermediate uveitis mimicking infectious endophthalmitis. All eyes were normotensive and presented with mild to moderate pain and predominantly moderate vitritis, associated with granulomatous keratic precipitates in 2 eyes and…

PURPOSE: To evaluate diabetic retinopathy (DR) screening global adherence rate and the association between sociodemographic and clinical variables and adherence rates to DR screening in individuals with diabetes. DESIGN: Systematic review and meta-analysis. METHODS: This systematic review was registered with International Prospective Register of Systematic Reviews (ID: CRD42024507035). We conducted a systematic review of relevant literature from inception of databases to February 24, 2024, using electronic databases searches including PubMed, MEDLINE (Ovid), EMBASE, Web of Science, Cochrane CENTRAL, and CDSR and national level DR screening databases through Google searches following PRISMA guidelines. The articles were screened for title and abstract and then for the full-text reports by two independent reviewers and study quality was appraised. Meta-analysis was performed using random effects model to calculate the pooled effects size and 95% confidence interval (CI) of each finding. RESULTS: Data from a total of 11,383,715 participants from 77 studies and two national websites…

Purpose To evaluate the safety and efficacy of subretinal gene therapy using AGTC-501 (rAAV2tYF-GRK1-RPGR) in male participants with X-linked retinitis pigmentosa (XLRP). Design Phase 1/2, open-label, dose-escalation study. Methods Setting: Four centers in the United States. Patient or Study Population: Twenty-nine males with XLRP and confirmed pathogenic RPGR variants. Mean age was 31.6 years (range 15-55). Intervention: Subretinal injection of AGTC-501 at doses ranging from 2.48 × 10 10 to 1.99 × 10 12 vg/eye administered in one eye per participant. Subretinal injection sites initially targeted the peripheral retina and then transitioned to the macula with successive cohorts. Main Outcome Measures: Treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), laboratory parameters, and immunological responses. Efficacy was evaluated by mesopic microperimetry mean sensitivity. Results All 29 participants experienced ≥1 TEAE. Eleven (38%) experienced ≥1 grade 3 TEAE. Six (21%) experienced ≥1 ocular SAE related to AGTC-501, including retinal detachment (n = 4),…

PURPOSE: To investigate the tear proteomic and neuromediator profiles, in vivo confocal microscopy (IVCM) imaging features, and clinical manifestations in neuropathic corneal pain (NCP) patients. DESIGN: Cross-sectional study. METHODS: A total of 20 NCP patients and 20 age-matched controls were recruited. All subjects were evaluated by corneal sensitivity, Schirmer test, tear break-up time, and corneal and ocular surface staining, Ocular Surface Disease Index and Ocular Pain Assessment Survey questionnaires were administered, as well as IVCM examinations for corneal nerves, microneruomas, and epithelial and dendritic cells. Tears were collected for neuromediator and proteomic analysis using enzyme-linked immunosorbent assay and data-independent acquisition mass spectrometry. RESULTS: Burning and sensitivity to light were the 2 most common symptoms in NCP. A total of 188 significantly dysregulated proteins, such as elevated metallothionein-2, creatine kinases B-type, vesicle-associated membrane protein 2, neurofilament light polypeptide, and myelin basic protein, were identified in…

PURPOSE: Identifying glaucoma patients at high risk of progression based on widely available structural data is an unmet task in clinical practice. We test the hypothesis that baseline or serial structural measures can predict visual field (VF) progression with deep learning (DL). DESIGN: Development of a DL algorithm to predict VF progression. METHODS: 3,079 eyes (1,765 patients) with various types of glaucoma and ≥5 VFs, and ≥3 years of follow-up from a tertiary academic center were included. Serial VF mean deviation (MD) rates of change were estimated with linear-regression. VF progression was defined as negative MD slope with p<0.05. A Siamese Neural Network with ResNet-152 backbone pre-trained on ImageNet was designed to predict VF progression using serial optic-disc photographs (ODP), and baseline retinal nerve fiber layer (RNFL) thickness. We tested the model on a separate dataset (427 eyes) with RNFL data from different OCT. The Main Outcome Measure was Area under ROC curve (AUC). RESULTS: Baseline average (SD) MD was 3.4 (4.9)dB. VF progression was detected in 900 eyes…

PURPOSE: To assess the efficacy of electronic health record (EHR) messaging for re-engaging patients with ophthalmology care after a missed appointment. DESIGN: Prospective, randomized clinical trial. METHODS: The study setting was an academic ophthalmology department. The patient population comprised of return patients age 18 years or older with an appointment "no show," or missed appointment. Over 2 phases of recruitment, 362 patients with an active patient portal in the EHR were selected consecutively each business day. Patients were randomized using a web-based tool to receive a reminder to reschedule via a standard mailed letter only (control) or the mailed letter plus an electronic message through the EHR within 1 business day of the missed appointment (intervention). Reengagement with eye care was defined as attendance of a rescheduled appointment within 30 days of the no-show visit. Patient charts were reviewed for demographic and clinical data. RESULTS: The average age of recruited patients was 59.9 years, just under half of the sample was male (42.5%, 154/362), and most…

PURPOSE: To evaluate the association between scleral thickness and a newly developed multimodal imaging-based classification of central serous chorioretinopathy (CSC). DESIGN: Retrospective, cross-sectional study. METHODS: This study included 217 eyes of 217 patients classified as simple or complex CSC based on the established protocols. Clinical and anatomical factors were compared between the 2 types. The scleral thickness was measured at 4 locations using anterior-segment optical coherence tomography. RESULTS: Of the 217 eyes, 167 were classified as simple CSC and 50 as complex CSC. The complex CSC group showed older age (P = .011), higher male ratio (P = .001), more bilateral involvement (P < .001), poorer visual acuity (P < .001), greater subfoveal choroidal thickness (P = .025), and higher frequency of loculation of fluid (P < .001) and ciliochoroidal effusion (P < .001) than the simple CSC group. The complex CSC group had significantly greater scleral thicknesses in the superior, temporal, inferior, and nasal directions (all P < .001) than the simple CSC group. Multivariable…

PURPOSE: To investigate the reduction of the ocular surface bacterial load induced by 2 commercially available ophthalmic antiseptic formulations, povidone-iodine (PVI) 0.6% and chlorhexidine (CLX) 0.02%, before ocular surgery. DESIGN: Randomized controlled trial. METHODS: Seventy adult patients undergoing intraocular surgery (phacoemulsification) were randomized to receive in the index eye PVI (group A) 4 times a day for 3 days or CLX (group B) 4 times a day for 3 days before surgery. The untreated eye was used as control. A conjunctival swab was taken in both eyes before (T0) and after (T1) therapy. Microbial DNA was quantified with real-time polymerase chain reaction (PCR) analysis. The Mick algorithm was used to compare the abundance of each genus/genera against the distribution of abundances from the reference. At T1, patients filled a questionnaire to evaluate therapy-induced symptoms. Primary outcome was the reduction of bacterial DNA at T1 (microbial load), vs control arm, expressed as mean number of real-time PCR cycle times (CTs). Secondary outcomes were taxonomic…

PURPOSE: To compare the effectiveness and safety of a novel binocular eye-tracking-based-home-treatment (CureSight) to patching for the treatment of amblyopia. DESIGN: Prospective, masked, multicenter randomized controlled trial. METHODS: One hundred forty-nine children 4 to < 9 years with anisometropic, small-angle strabismic, or mixed-mechanism amblyopia were randomized to either binocular dichoptic treatment (n=75) or patching (n=74). The binocular dichoptic treatment group used the CureSight system for 90 min/day, 5 days/week for 16 weeks (120 hours). The patching group received 2-hour patching 7 days/week (224 hours). The primary outcome was the mean improvement from baseline in amblyopic eye visual acuity (VA) to week 16 in both study groups (non-inferiority of ≤0.10 logarithm of the minimum angle of resolution [logMAR]). RESULTS: In the modified intent-to-treat (mITT) group, the mean improvement from baseline at week 16 in the binocular treatment group was noninferior to patching group improvement (0.034 logMAR [95% CI -0.009 to 0.076]). In the per-protocol (PP) dataset, the…

PURPOSE: This study sought to identify the most effective testing program for detecting visual-field defects in mild-stage glaucoma with central visual-field defects. DESIGN: A multicenter, retrospective diagnostic testing evaluation. PARTICIPANTS: The study involved 93 eyes (83 patients) with mild-stage glaucoma (median mean deviation [interquartile range]: -1.79 [2.16] dB) with central visual-field defects and 69 eyes (63 patients; median mean deviation, -1.38 [2.31] dB) with mild-stage glaucoma without central visual-field defects, from Jikei University School of Medicine and Tajimi Iwase Eye Clinic. METHODS: Patients underwent 10-2 Swedish Interactive Thresholding Algorithm (SITA) Standard, 24-2 SITA Standard, and 24-2C SITA Faster tests. Central visual-field defects were defined using 10-2 SITA Standard and optical coherence tomography (OCT). A detection power of 4 points in the 24-2 that coincided with 10-2 (Center4), 12 points that lie within 10° (24-2-12), and 22 points that lie within 10° of 24-2C (24-2C-22) were analyzed using receiver operating characteristic (ROC) curves…

PURPOSE: The SPECTRUM 4 and 3 studies assessed the intraocular pressure (IOP)-lowering efficacy and safety of omidenepag isopropyl (OMDI) 0.002% vs timolol 0.5% in patients with glaucoma or ocular hypertension (OHT). DESIGN: Phase 3, randomized, controlled, double-masked, noninferiority studies. METHODS: Multicenter studies in the US. Inclusion criteria for adults ≥ 18 years (SPECTRUM 4 [N = 409] and 3 [N = 413]) were open-angle glaucoma or OHT, and IOP ≥ 22 mm Hg and ≤ 34 mm Hg; and for pediatric patients < 18 years (N = 13, SPECTRUM 3) were pediatric glaucoma or OHT. The primary objective in both studies was OMDI noninferiority to timolol in reducing IOP (3 months). SPECTRUM 3 included an additional 9 months of OMDI treatment. Safety evaluations were of ocular/non-ocular adverse events (AEs). RESULTS: The IOP-lowering range of OMDI remained consistent in SPECTRUM 4 and 3 (-5.6 to -5.9 vs -5.3 to -5.7 mm Hg, respectively); however, timolol efficacy varied (-5.4 to -6.1 vs -6.4 to -7.0 mm Hg, respectively). OMDI noninferiority was achieved in SPECTRUM 4. Efficacy was maintained with…

PURPOSE: To evaluate visual outcomes and patient-reported results after bilateral femtosecond-laser-assisted refractive lens exchange (RLE) with the implantation of a diffractive trifocal intraocular lens. DESIGN: Prospective interventional case series. METHODS: A study of 27 patients (54 eyes) implanted with the Clareon PanOptix (Alcon) multifocal intraocular lens during femtosecond-laser-assisted RLE in a university hospital setting. The uncorrected (UDVA) and corrected (CDVA) distance visual acuity, uncorrected (UIVA) and distance-corrected (DCIVA) intermediate visual acuity at 60 cm, uncorrected (UNVA) and distance-corrected (DCNVA) near visual acuity at 40 and 33 cm were evaluated at 3 months postoperatively and compared with the preoperative values. In addition, we assessed the postoperative defocus curve, mesopic and photopic contrast sensitivity, and patient-reported spectacle independence. RESULTS: The mean postoperative binocular UDVA was -0.02 ± 0.06 logMAR and CDVA was -0.11 ± 0.05 logMAR. The UIVA was -0.07 ± 0.05 logMAR and DCIVA was -0.07 ± 0.07 logMAR. The UNVA at 40…

PURPOSE: To evaluate the predictive accuracy of modern intraocular lens (IOL) formulas and axial length (AL) adjusted traditional IOL formulas, including Wang-Koch and Cooke-modified AL (CMAL) method, in long eyes with plate-haptic IOLs, and to compare refractive prediction error variances with C-loop IOLs. DESIGN: Retrospective consecutive case series study. METHODS: Data from 391 eyes with Zeiss 509 M and 302 eyes with Alcon SN6CWS implants in highly myopic patients, following cataract surgery from January 2019 to November 2023, were collected. One eye per patient was selected. Predictive outcomes of 15 modern formulas (Barrett Universal II (BU II), Cooke K6 (K6), Emmetropia Verifying Optical (EVO) 2.0, Hoffer-QST, Kane, Karmona, Ladas AI, Naeser 2, Olsen, Pearl-DGS, Radial Basis Function (RBF) 3.0, T2, VRF-G, Zhu-Lu, and Z-Calc) and 4 traditional IOL formulas (Haigis, Hoffer Q, Holladay 1, and SRK/T) with AL adjusted methods, were evaluated. The mean prediction error, mean absolute prediction error (MAE), root-mean-square absolute prediction error (RMSAE) and the proportions of…

PURPOSE: To explore the incidence of antibodies against adalimumab (AAA) development in noninfectious uveitis (NIU) and to examine the impact of treatment adjustment in nonresponders. DESIGN: Retrospective case series. METHODS: In this single-center study of patients with NIU treated with adalimumab, blood samples for adalimumab and AAA were collected and therapeutic adjustments post-monitoring in non-responders were analyzed including changes in injection intervals, addition of conventional disease-modifying antirheumatic drugs (cDMARD), and treatment alterations to biologic DMARD. The main outcome measures were the proportion of patients with positive AAA and active uveitis, decrease of AAA at final follow-up by different therapeutic interventions. RESULTS: Of 42 patients who underwent laboratory investigations at 17.9 months after adalimumab initiation, 22 (52.4%) patients who were nonresponders demonstrated AAA (1243 ng/mL) with a mean adalimumab trough level of 3.0 µg/mL, significantly lower than the mean drug levels of patients without AAA (11.8 µg/mL). Fifteen (35.7%)…

PURPOSE: To compare intraindividual monocular visual performance of a monofocal extended depth-of-focus (EDOF) and a trifocal EDOF intraocular lens (IOL) following bilateral cataract surgery. DESIGN: Single-center, prospective, fellow-eye comparison clinical trial. METHODS: All patients received uneventful bilateral cataract surgery with implantation of the monofocal EDOF Isopure IOL in the dominant eye and the trifocal EDOF FineVision Triumf IOL in the nondominant eye. Intraindividual monocular comparison included visual acuity at various distances, defocus curves, internal total higher-order aberration (HOA), spherical aberration (SA) Z(4.0), IOL decentration, and tilt. Additionally, subjective outcomes were evaluated using Halo and Glare simulation and the Seven-Item Visual-Functioning Index questionnaire. RESULTS: In total, 25 patients (50 eyes) were included. Intraindividual monocular best-corrected distance visual acuity, distance-corrected intermediate visual acuity, and best-corrected near visual acuity were comparable (P > .05). However, monocular contrast acuity (P =…

PURPOSE: Investigating the relationship between cardiovascular health (CVH) and retinopathy in the adult population of the United States. DESIGN: The cross-sectional study. METHODS: The study utilized samples, including the diabetes population, from the National Health and Nutrition Examination Survey (NHANES) conducted between 2005 and 2008 (N= 4249), to assess cardiovascular health (CVH) using the Life's Essential 8 (LE8) assessment. Retinopathy is determined through imaging assessment by professionals independently grading fundus photographs. Univariable and multivariable weighted logistic regression models, restricted cubic splines (RCS), subgroup analysis and weighted quantile sum (WQS) regression approaches were employed to assess the association between LE8 score-based CVH status and retinopathy. The mediation analysis was conducted to investigate whether serum albumin levels mediated the relationship between LE8 score and retinopathy. RESULTS: In a fully adjusted logistic regression model, participants in the moderate and high CVH groups had a 39% (odds ratio (OR) 0.61, 95%…