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Joseph M Coney,1 Jasmyne E McCoy,1 Samriddhi Buxy Sinha,2 Nina Sonbolian,2 Lujia Zhou,3 Thomas P Hull,1 Shawn A Lewis,1 David G Miller,1 Michael A Novak,1 Scott D Pendergast,1 Hang Pham,1 Sean M Platt,1 Llewelyn J Rao,1 Jerome P Schartman,1 Lawrence J Singerman,1 Richard Donkor,1 Margaret Fink,1 Ryan Zubricky,4 Helene Karcher2 1Retina Associates of Cleveland Inc, Beachwood, OH, USA; 2Novartis Pharma AG, Basel, Switzerland; 3KMK Consulting, Morristown, NJ, USA; 4Geisinger Eye Institute, Danville, PA, USACorrespondence: Joseph M Coney, Retina Associates of Cleveland Inc, 24075 Commerce Park, Beachwood, OH, 44122, USA, Tel +1 (216) 831-5700, Email jconey@retina-assoc.comObjective: Retrospective, real-world study to evaluate visual acuity (VA), anti-vascular endothelial growth factor (anti-VEGF) injection intervals, and central macular thickness (CMT) in neovascular age-related macular degeneration (nAMD) eyes switched to brolucizumab only or to brolucizumab alternating with another anti-VEGF.Methods: The overall study population comprised eyes that were given ≥ 1 brolucizumab injection between 1 October 2019 and 30 November 2021. The brolucizumab-only (BRO) cohort consisted of prior anti-VEGF-treated eyes treated exclusively with ≥ 3 brolucizumab injections over ≥ 12 or ≥ 18 months; the alternating brolucizumab (ALT) cohort comprised prior anti-VEGF-treated eyes treated with ≥ 2 brolucizumab injections and ≥ 1 other anti-VEGF over ≥ 12 or ≥ 18 months.Results: A total of 482 eyes received ≥ 1 brolucizumab injection during the study period. Mean VA changes from baseline were − 1.1± 15.1 letters (BRO cohort; n = 174) and 1.3± 13.0 letters (ALT cohort; n = 47) at Month 12, and 0.0± 13.5 letters (BRO cohort; n = 95) and − 7.3± 17.2 letters (ALT cohort; n = 29) at Month 18. Mean changes in injection intervals were +26.9± 48.1 days (BRO cohort) and +11.1± 17.3 days (ALT cohort) at Month 12 and +36.3± 52.3 days (BRO cohort) and +14.0± 19.9 days (ALT cohort) at Month 18. Mean changes in CMT were − 35.2± 108.1 μm (BRO cohort) and − 31.5± 91.2 μm (ALT cohort) at Month 12 and − 38.9± 75.0 μm (BRO cohort) and − 9.0± 59.9 μm (ALT cohort) at Month 18. Intraocular inflammation-related adverse events were recorded in 22/482 (4.6%) eyes.Conclusion: Treatment with either brolucizumab alone or brolucizumab alternating with another anti-VEGF can preserve vision, reduce CMT, and extend anti-VEGF injection intervals in patients with nAMD.Keywords: alternating anti-VEGF treatments, brolucizumab, neovascular age-related macular degeneration, wet age-related macular degeneration, 12-month outcomes, 18-month outcomes

Purpose: To examine the relationship between systemic arterial blood pressure (BP) and the rate of change in standard automated perimetry (SAP) in eyes with glaucoma and suspected glaucoma., Design: Prospective cohort study., Participants: One hundred twenty-four eyes (91 eyes with glaucoma, 33 eyes with suspected glaucoma) of 64 patients (mean age, 68.4 ± 7.6 years) followed up at the Bascom Palmer Eye Institute, Palm Beach Gardens, Florida., Methods: Participants underwent ophthalmic examination, BP measurement, and SAP at 4-month intervals. At the baseline visit, 24-hour ambulatory blood pressure monitoring (ABPM) was acquired. Linear mixed models (adjusted for inclusion of both eyes, age, sex, race, intraocular pressure, baseline severity, and central corneal thickness) were used to investigate the effect of BP on the rates of SAP mean deviation (MD) change over time., Main Outcome Measures: Effect of baseline 24-hour and follow-up mean arterial pressure (MAP), systolic BP (SBP), and diastolic BP on change in SAP MD., Results: Eyes underwent an average of 8.9 ± 1.5 SAP examinations over 28.3 ± 6.0 months of follow-up. The median rate of MD change was 0.14 dB/year (range, -1.21 to 0.96 dB/year) with 9 eyes (7%) showing moderate to fast progression (MD change, ≤ -0.50 dB/year). Each 10 mmHg lower in 24-hour average MAP and SBP were associated with -0.171 dB/year (P = 0.045) and -0.137 dB/year (P = 0.023) faster rates of MD loss. Lower mean SBP during follow-up was associated significantly (P = 0.003) with MD progression., Conclusions: Lower baseline 24-hour ABPM measurements, as well as low SBP during follow-up, were associated significantly with faster rates of glaucomatous SAP progression and may be used as a predictor of risk of glaucomatous progression., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: Prescribers must possess extensive knowledge and maintain a positive attitude towards the rational use of medicines to achieve desirable treatment outcomes and effectively prevent treatment failures, increased costs, drug toxicities, and interactions. The objective of this study was to evaluate prescribers' understanding and perception concerning the rational use of medicines in public hospitals. Additionally, the study aimed to identify the factors that influence rational prescribing practices., Methods: A structured data instrument was developed to collect demographic data and evaluate participants' knowledge and perception of rational medicine use, in line with the study objectives. Chi-squared statistics and Fisher's exact test were utilized to identify factors associated with good knowledge and perception among participants. Logistic regression was then employed to assess the strength of the associations, with odd ratios reported at a significant level of 0.05., Results: Out of 192 participants, 85.4% held a positive view of rational medicine use, stressing patient safety and recognizing risks like antimicrobial resistance and polypharmacy. Perception was influenced by factors such as prescriber profession, access to references, and drug bulletin updates. Additionally, 65.6% demonstrated good knowledge of rational medicine use, which was notably influenced by factors like using standard prescribing guidelines, having a functional Drug and Therapeutics Committee, prescriber profession, and the frequency of drug bulletin updates., Conclusion: The study emphasizes the critical need to address knowledge gaps among healthcare professionals, especially nurses and other prescribers, to ensure the safe and effective use of medications. It highlights the positive influence of utilizing preferred prescribing references and the existence of functional Drug and Therapeutics Committees in hospitals on knowledge levels. However, the unexpected findings regarding the limited impact of frequent updates of drug bulletins require further investigation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Djochie et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: This study evaluated changes in best-corrected visual acuity and submacular hemorrhage (SMH) resolution in eyes after a single rapid subretinal displacement surgery using subretinal balanced saline solution and sterile air without tissue plasminogen activator (tPA)., Design: A retrospective comparative interventional analysis., Participants: Twenty-six eyes with thick SMH who underwent pars plana vitrectomy and subretinal fluid displacement without tPA from 2015 and 2021 and at least 1-year of follow-up., Methods: Surgical intervention included a standard small-gauge pars plana vitrectomy with subretinal displacement using balanced saline solution with subretinal sterile air and partial gas-air fluid exchange. Main outcome measures included degree of subfoveal SMH displacement, best and final postoperative visual acuities, and adverse events. Snellen acuity was converted to logMARs for statistical analysis., Results: The most common etiology associated with thick SMH (92.3%) was neovascular age-related macular degeneration. Within 1 month postoperatively, 21 patients (80.8%) saw complete subfoveal blood displacement. Most of the SMH surgical displacements were done within 1 week of presenting symptoms. Average preoperative duration of SMH was 3.60 ± 2.78 days (range, 1-12 days). Mean logMAR best-corrected visual acuity improved from 1.63 ± 0.58 (Snellen 20/800 baseline) to 0.90 ± 0.42 letters (Snellen 20/160) at last follow-up (p = 0.001). This study's visual acuity improvement is comparable with that of prior studies using tPA. Early postoperative complications included 1 retinal detachment, 1 vitreous hemorrhage, and 1 macular hole., Conclusion: Rapid surgery with subretinal balanced saline solution-sterile air injection without tPA was found to be effective for displacement of thick SMH with retinal function, visual acuity, and corneal refractive therapy improvement., (Published by Elsevier Inc.)

Importance: Intra-arterial chemotherapy (IAC) has quickly gained popularity as a mainstay of treatment for retinoblastoma. Intra-arterial chemotherapy has been described as having several advantages over systemic chemotherapy, including reducing systemic toxicity and neutropenia; however, studies on the risk of neutropenia after IAC remain limited., Objective: To estimate the incidence of neutropenia after IAC, as well as identify risk factors associated with the development of neutropenia., Design, Setting, and Participants: This case series included pediatric patients with unilateral or bilateral retinoblastoma who were treated with IAC at a single quaternary care center from July 13, 2013, to January 6, 2023., Exposure: All patients were treated with IAC and underwent multiple IAC cycles depending on treatment response. The primary chemotherapy agent used was melphalan, but topotecan or carboplatin could be used along with melphalan. Melphalan doses were kept to 0.4 mg/kg or less per cycle. After each IAC cycle, complete blood cell counts were obtained within 10 to 12 days and repeated until the absolute neutrophil count (ANC) was greater than or equal to 1000/μL., Main Outcomes and Measures: The primary outcome was the minimum ANC after each IAC cycle. The secondary outcome was the development of severe (grade 3 or 4) neutropenia (ANC <1000/μL). Regression analyses were used to identify associations between variables and outcomes. Receiver operating characteristic curves were used to calculate threshold dose for each chemotherapy agent potentially associated with the development of severe neutropenia., Results: A total of 64 eyes of 49 patients (mean [SD] age, 1.7 [1.2] years; 25 females [51.0%]) with retinoblastoma were treated with 171 cycles of IAC. The mean (SD) nadir ANC was 1325.3 (890.7)/μL and occurred a median (IQR) of 10 (10-14) days (range, 6-28 days) after IAC administration. The frequency distribution of post-IAC neutropenia grades 0, 1, 2, 3, 4, and missing was 31 (18.1% of cycles), 25 (14.6%), 40 (23.4%), 37 (21.6%), 26 (15.2%), and 12 (7.0%), respectively. Factors weakly correlated with a lower ANC were higher melphalan dose (β = -2356 [95% CI, -4120.6 to -611.2]; adjusted R2 = 0.251; P = .01) and higher topotecan dose (β = -4056 [95% CI, -7003.6 to -1344.5]; adjusted R2 = 0.251; P = .006)., Conclusions and Relevance: In this case series of patients with retinoblastoma, the incidence of severe neutropenia after IAC was nearly 40%, which is higher than previously reported. Extended laboratory monitoring may aid in capturing previously overlooked cases of neutropenia. Topotecan may be associated with the development of neutropenia; limiting topotecan doses, especially in the setting of a high melphalan dose, may be beneficial in reducing the risk of neutropenia.

Introduction: Intraocular inflammation (IOI)-related adverse events (AEs) that may result in severe vision loss have been associated with the anti-vascular endothelial growth factor brolucizumab. In this study, we investigate the timing, management and resolution of IOI-related AEs in a large cohort of patients treated with at least one injection of brolucizumab in routine clinical practice., Methods: Retrospective review of medical records from patients with neovascular age-related macular degeneration treated with ≥ 1 brolucizumab injection between October 2019 and November 2021 at the Retina Associates of Cleveland, Inc. clinics., Results: Of the 482 eyes included in the study, IOI-related AEs occurred in 22 (4.6%) eyes. Four (0.8%) eyes developed retinal vasculitis (RV) and of these, 2 (0.4%) had concomitant retinal vascular occlusion (RO). Most eyes [14/22 (64%)] developed the AE within 3 months and 4/22 (18%) within 3-6 months of the first brolucizumab injection. The median [interquartile range (IQR)] time from the last brolucizumab injection to development of the IOI-related AE was 13 (4-34) days. At the time of event, 3 (0.6%) eyes with IOI (no RV/RO) developed severe vision loss of ≥ 30 ETDRS letters, and a further 5 (1.0%) eyes (1 with IOI + RV, 1 with IOI + RV + RO) developed moderate vision loss of ≥ 15 letters compared with their last visual acuity (VA) prior to the AE. The median (IQR) vision loss was -6.8 (-19.9, -0.0) letters. Taking the best VA at either 3 or 6 months after AE resolution (or stability for occlusive events), VA decreased by ≥ 5 letters compared with prior to the AE in 3 (14%) of the 22 affected eyes, and was preserved (< 5-letter loss) in 18 (82%) eyes., Conclusions: In this real-world study, most IOI-related AEs occurred early after brolucizumab treatment initiation. With appropriate monitoring and management of IOI-related AEs, vision loss associated with brolucizumab may be limited., (© 2023. The Author(s).)

The objective of this review was to estimate the prevalence of strabismus and amblyopia in Africa. A systematic online literature search was conducted for articles on strabismus and amblyopia in Africa. Meta-analysis was performed, using the Freeman-Tukey double arcsine transformation, to estimate the prevalence of strabismus and amblyopia in Africa. Subgroup analyses were conducted according to age, gender, study year, and type of amblyopia. Meta-regression was used to evaluate the influence of predetermined factors on the prevalence of amblyopia. 8 (1 population-based & 7 school-based) and 21 (3 population-based & 18 school-based) studies on strabismus and amblyopia with sample sizes of 22,355 and 46,841, respectively, were included in the review. Overall prevalence of strabismus in Africa was estimated to be 0.8% (95% CI: 0.4% - 1.4%); exotropia was 0.2% (95% CI: 0.1% - 0.5%) and esotropia was 0.5% (95% CI: 0.1% - 1.2%). Overall prevalence of amblyopia was estimated to be 0.6% (95% CI: 0.3% - 0.9%); refractive and strabismic amblyopia were 1.1% (95% CI: 0.2% - 2.5%) and 0.4% (95% CI: 0.2% - 0.6%), respectively. Prevalence estimate of amblyopia in males was 1.8% (95% CI: 0.7% - 3.3%) and in females was 1.3% (95% CI: 0.4% - 2.6%). There was a significant association between the prevalence of amblyopia and the type of amblyopia (p = .007) and the study year (p = .006). Although there appears to be a relatively low prevalence of strabismus and amblyopia in Africa, there is a dearth of well-designed population-based studies on strabismus and amblyopia in Africa, resulting in the lack of epidemiological information on strabismus and amblyopia within the general African population. Information about the prevalence of strabismus and amblyopia across Africa can inform policy making and design and implementation of public health intervention program.

Background: The anti-vascular endothelial growth factor (anti-VEGF) injection interval influences treatment burden and compliance in neovascular age-related macular degeneration (nAMD). This real-world study investigates visual acuity (VA), injection-interval extension, central macular thickness (CMT) and safety in nAMD eyes switched to the anti-VEGF agent brolucizumab and followed for up to 18 months., Methods: This retrospective study included patients with nAMD who were switched from other anti-VEGF agents to brolucizumab only. Patient eyes were grouped into three nested cohorts with the overall cohort receiving ≥ 1 brolucizumab injection, the second receiving ≥ 3 brolucizumab injections with a follow-up period of ≥ 12 months and the third cohort receiving ≥ 3 brolucizumab injections with a follow-up period of ≥ 18 months. Study endpoints included changes from baseline at 12 or 18 months in VA, injection intervals, and CMT. Sub-group analyses were conducted using baseline injection interval length or baseline VA as qualifiers., Results: Overall, 482 eyes received ≥ 1 brolucizumab injection; 174 eyes received ≥ 3 brolucizumab injections with ≥ 12 months of follow-up, and 95 eyes received ≥ 3 brolucizumab injections with ≥ 18 months of follow-up. VA (mean [95% confidence intervals]) remained stable relative to baseline after 12 months (- 1.1 [- 3.7, 1.6] letters; p = 0.42) and 18 months (0.0 [- 3.1, 3.1] letters; p = 0.98) of brolucizumab treatment, respectively, and pre-switch injection intervals or baseline VA had no notable effect. Following the switch to brolucizumab, injection intervals were extended from baseline to month 12 by 26.9 (19.7, 34.0) days (p < 0.0001), and eyes with pre-switch injection intervals < 8 weeks were able to have their injection intervals extended by 23.6 days longer than eyes with pre-switch injection intervals ≥ 8 weeks. At 18 months, injection intervals were extended by 36.3 (25.6, 46.9) days (p < 0.0001) compared to baseline. Following switch to brolucizumab, CMT was reduced at both 12 and 18 months (12 months: - 35.2 (- 51.7, - 18.8) µm, p < 0.0001; 18 months: - 38.9 (- 54.3, - 22.0) µm, p < 0.0001). Intraocular inflammation-related adverse events were reported in 4.6% of brolucizumab-treated eyes., Conclusions: This real-world study demonstrates that injection intervals may be significantly extended with maintained vision and reduced CMT in nAMD eyes switching to brolucizumab therapy from other anti-VEGFs., (© 2023. The Author(s).)

Purpose: To estimate the prevalence of keratoconus in tertiary eye care facilities in Ghana., Methods and Analysis: In this hospital-based retrospective cohort study, medical records of patients from tertiary/referral eye care facilities in Ghana were reviewed. Included in the study were records of individuals who visited the eye care facilities and were diagnosed of keratoconus within the period of January 2016 to December 2019 inclusive. Data on patients' demographics, severity of keratoconus, mode of diagnosis, treatment, and visual acuity outcomes were analysed., Results: Out of the total of 142,209 records reviewed, 75 patients were diagnosed of keratoconus in at least one eye (127 eyes; 86.8% bilateral cases), representing a prevalence estimate of 53 per 100000 (95% confidence interval (CI): 41 to 65 per 100000). The mean ± SD age of patients at the time of diagnosis was 21.1 ± 9.5 years (66.2% males). The mean ± SD keratometry in keratoconus patients was 52.1 ± 7.0: majority (76.5%) of the cases were moderate to severe keratoconus. The main primary treatment regimen was corneal transplant (58.8%) followed by spectacles (25.0%), crosslinking (8.8%) and rigid contact lens (7.3%). There was a significant association between post-treatment visual acuity outcomes and treatment type (p < 0.001)., Conclusion: Our study represents the first prevalence estimate of keratoconus in Ghana. The prevalence of keratoconus estimated in our study is lower than that reported in countries with tropical climates. This could be due to lower uptake of referrals, underdiagnosis and/or misdiagnosis of the condition in lower-level health facilities.

Purpose: To review and summarize information on meibomian gland dysfunction (MGD) epidemiology in Africa., Methods: A systematic search of online databases was conducted for literature/studies on MGD in Africa. Meta-analysis was conducted to estimate the prevalence of MGD in Africa. Meta-regression was used to explore sources of heterogeneity., Results: Twelve studies conducted in five countries were included in the review. All studies were hospital-based studies. Nine studies were included in the meta-analysis; the total sample size was 4963 and participants' age range was 17-96 years. The overall prevalence estimate of MGD in Africa was 45.9% (95% CI: 27.6-64.1%). Prevalence of MGD among males and females were each pooled from three studies and in urban and rural setting from 6 and 3 studies, respectively. Prevalence of MGD among males and females were 56.0% (95% CI: 22.4-89.5%) and 58.9% (95% CI: 28.5-89.4%) respectively; in urban and rural settings were 42.8% (95% CI: 21.1-64.5%) and 65.7% (95% CI: 25.7-95.7%), respectively. There was no association of MGD with sex ( p = .872) and with study setting ( p = .231)., Conclusion: There is a paucity of evidence on MGD prevalence in Africa, emphasizing the need for epidemiological studies to enhance our understanding of region-specific differences in MGD in Africa. The pooled estimate from hospital-based studies, however, suggests a substantial MGD burden in Africa. Epidemiological studies are needed to assess if this translates to a high disease burden within the general African population.