Intravitreal Infliximab for the Treatment of Proliferative Vitreoretinopathy (FIXER): A Randomized Controlled Phase II Trial.

OBJECTIVE: To study the safety and efficacy of intravitreal infliximab administered at the conclusion of pars plana vitrectomy (PPV) in the treatment of proliferative vitreoretinopathy (PVR) associated with rhegmatogenous retinal detachment (RRD). DESIGN: Randomized controlled phase II clinical trial. SUBJECTS: Patients with primary RRD and grade C PVR, according to the updated Retina Society Classification. METHODS: Sixty-six patients were randomized in a 1:1 ratio to undergo PPV and silicone oil (SO) injection with or without intravitreal injection of 1 mg/0.05 mL of infliximab in the air-filled globe before SO injection at PPV conclusion. Surgeons were masked to treatment allocation until PPV conclusion. MAIN OUTCOME MEASURES: The primary outcome measure was anatomic success (defined as complete retinal reattachment without a tamponade at 6 months post SO removal). Secondary outcome measures were final best-corrected visual acuity (BCVA), single-operation success rate (SOSR), rate of recurrent detachment, central macular thickness (CMT) by macular OCT, macular function by multifocal electroretinogram, and macular vascular density (VD) by OCT angiography. RESULTS: Sixty eyes of 60 patients, 30 eyes in each group, completed the study. At baseline, there were no differences regarding age, gender, history of trauma, lens status, duration of RRD, BCVA, intraocular pressure (IOP), intraocular inflammation (IOI), detachment extent in clock hours, number/size of breaks, presence of vitreous hemorrhage, axial length, or grade/extent of PVR between both groups. For the outcome measures, 30 eyes in the infliximab group achieved anatomic success vs. 29 eyes in the control group. The SOSR was higher in the infliximab group (26) vs. the control (23), but this was not statistically significant (P = 0.317). Final logarithm of the minimum angle of resolution BCVA was better in the infliximab group (mean, 0.96; standard deviation [SD], 0.4; Snellen equivalent ≈ 20/180) vs. the control (mean, 1.14; SD, 0.4); Snellen equivalent ≈ 20/280; P = 0.044). There were no differences regarding IOP, IOI, time of SO removal, macular function, CMT, or VD. CONCLUSIONS: Pars plana vitrectomy with SO tamponade with or without intravitreal infliximab is effective in treating PVR-associated RRD. Infliximab may be associated with modest improvement in final visual outcomes but not anatomic outcomes. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

Quality, Reliability, Readability, and Accountability of Online Information on Leukocoria.

PURPOSE: To evaluate the quality, reliability, and readability of online patient educational materials on leukocoria. METHODS: In this cross-sectional study, the Google search engine was searched for the terms "leukocoria" and "white pupil." The first 50 search outcomes were evaluated for each search term based on predefined inclusion criteria, excluding duplicates, peer-reviewed papers, forum posts, paywalled content, and multimedia links. Sources were categorized as "institutional" or "private." Three independent raters assessed each website for quality and reliability using DISCERN, Health on the Net Code of Conduct (HONcode), and JAMA criteria. Readability was evaluated using seven formulas: Flesch Reading Ease (FRE), Flesch-Kincaid Grade Level (FKGL), Simple Measure of Gobbledygook (SMOG) Index, Automated Readability Index (ARI), Linsear Write (LW), Gunning Fog Index (GFI), and Coleman-Liau Index (CLI). RESULTS: A total of 51 websites were included. Quality, assessed by the DISCERN tool, showed a median score of 4, denoting moderate to high quality, with no significant differences between institutional and private sites or search terms. HONcode scores indicated variable reliability and trustworthiness (median: 10, range: 3 to 16), with institutional sites excelling in financial disclosure and ad differentiation. Additionally, institutional and private sites performed well in reliability and accountability, as measured by the JAMA Benchmark criteria (median: 3; range: 1 to 4). Readability, averaging an 11.3 ± 3.7 grade level, did not differ significantly between site types or search terms, consistently falling short of the recommended sixth-grade level for patient educational materials. CONCLUSIONS: The patient educational materials on leukocoria demonstrated moderate to high quality, commendable reliability, and accountability. However, the readability scores were above the recommended level for the layperson. [J Pediatr Ophthalmol Strabismus. 20XX;X(X):XX-XX.].

Pediatric and Adolescent Traumatic Macular Hole: A Systematic Review.

PURPOSE: The optimal management of pediatric traumatic macular holes (TMH) is unclear from lack of prospective randomized trials. The literature is divided into early (≤1month post-trauma), delayed (>1 month) pars plana vitrectomy (PPV), and observation. Our aim is to find which group can achieve best-superior spectacle corrected visual acuity (VA), visual gain, and time for hole closure. DESIGN: Systematic review. METHODS: This systematic review was registered with PROSPERO (ID:CRD42022383134). The databases searched from inception until July 31, 2023, were MEDLINE OVID, Scopus, Web of Science, Embase, and Google Scholar. The articles were screened for title and abstract then for full text. Risk of bias was also assessed. Three outcome measures were analyzed: final VA, visual gain, and time to closure of macular hole (MH). MH size was divided into small (≤250 µm), medium (>250-500 µm), and large (>500 µm). RESULTS: Ninety eight (98) studies with 234 patients in the PPV group and 87 patients in the observation group were included in the review. Final VA (logarithm of the minimum angle of resolution) and visual gain were respectively in PPV vs observation groups: (1) small MH 0.37 ± 0.52 vs 0.42 ± 0.56 (P = .484) and -0.96 ± 0.83 vs -0.49 ± 0.40 (P = .005); (2) medium MH 0.58 ± 0.39 vs 0.34 ± 0.34 (P = .06) and -0.36 ± 0.42 vs -0.74 ± 0.44 (P < .001); (3) large MH 0.62 ± 0.42 vs 0.59 ± 0.35 (P = .337) and -0.31 ± 0.48 vs -0.62 ± 0.37 (P = .11). Small TMH had comparable closure time: 3.21 ± 2.52 months vs 3.49 ± 4.43 (P = .954) in the PPV and observation groups. Early and late PPV yielded comparable final VA 0.67 ± 0.66 vs 0.54 ± 0.35 (P = .576) and visual gain -0.58 ± 0.69 vs -0.49 ± 0.48 (P = .242) in the PPV and observation groups. CONCLUSIONS: PPV was very effective in closing TMH and VA gain in children throughout a wide range of hole size. Early and delayed PPV yielded similar anatomic and visual results. Observation and PPV yielded comparable final VA and closure time. Clinicians can choose either early PPV or delayed PPV when healing biomarkers are absent on periodic optical coherence tomography.

The Characteristics of White Dot Syndromes Following SARS-COV-2 Infection: A Systematic Review.

PURPOSE: To review all studies reporting the occurrence of white dot syndromes (WDSs) following SARS-COV-2 infection. METHODS: On May 12, 2023, we registered our protocol on PROSPERO [registration number: CRD42023426012]. Five different databases including PubMed, Scopus, Web of Science, Google Scholar, and Science Direct were searched up to May 2023. We included all studies that reported the symptoms of WDSs following SARS-COV-2 infection. The data was extracted using a uniform Excel extraction sheet. All statistical tests were conducted with a 95% confidence interval and a 5% error margin. A p-value of less than 0.05 was considered statistically significant. The publication bias of included studies was assessed using JBI Critical Appraisal Checklist for Case Reports and IHE Quality Appraisal Checklist for Case Series studies. RESULTS: This review included thirty-two studies involving forty-eight patients. Acute macular neuroretinopathy was the most common disease (70.8%) followed by multiple evanescent white dot syndrome (14.6%) with 58.3% of WDS after their first SARS-COV-2 infection, and paracentral acute middle maculopathy (4.1%). They were mostly unilateral (56.2%). The presenting symptoms were blurred vision (70.8%), visual field disturbance (68.7%), and photopsia (20.8%). About 35.4% of the patients improved by their treatment and future complications were persistent scotoma (4.2%) and macular edema (2.1%). CONCLUSION: White dot syndromes are very rare entities. Our findings suggest a possible association between white dot syndrome onset and SARS-COV-2 infection. We recommend ophthalmologists should be aware of this suggested association to deliver better management and patients' care.

Retinal Pigment Epithelial Adenoma: Initial Treatment Outcomes following Episcleral Brachytherapy.

Introduction: We aim to explore the safety and efficacy of episcleral brachytherapy as a primary management option for eyes with retinal pigment epithelial (RPE) adenoma. Methods: Retrospective chart review of the demographic, clinical, ancillary, and postoperative outcome data of patients with RPE adenoma in 2 tertiary referral centers. Tumor regression, final visual acuity, and complications were assessed. Results: Five patients (3 females and 2 males) were included. Four of the 5 eyes had peripheral and mid-peripheral lesions, while one tumor was juxtapapillary. Three eyes were treated with ruthenium-106 (100 Gray), and 2 received iodine-125 episcleral plaques (85 Gray). All eyes showed clinical and imaging-based evidence of regression. Four eyes had stable or improved visual acuity, while 1 eye exhibited one line loss of visual acuity due to radiation retinopathy. Local recurrence was not observed in any eye over a median follow-up of 24 (range 6-112) months. Conclusions: Episcleral brachytherapy is an effective management option for select cases of RPE adenoma that is capable of achieving tumor regression while maintaining favorable visual acuity. The initial safety profile of brachytherapy is good without significant vision-compromising complications.

The characteristics of white dot syndromes following COVID-19 Vaccines: a systematic review.

PURPOSE: To review all studies reporting the onset of white dot syndromes following COVID-19 vaccines. METHODS: Our protocol was registered prospectively on PROSPERO [registration number: CRD42023426012]. We searched five different databases including PubMed, Scopus, Web of Science, Google Scholar, and Science Direct up to May 2023. All the studies that reported the occurrence of white dot syndrome following COVID-19 vaccines were included. All statistical tests were conducted with a 95% confidence interval and a 5% error margin. A p value of less than 0.05 was considered statistically significant. The methodological quality of included studies was performed using the IHE Quality Appraisal Checklist for Case Series studies and JBI Critical Appraisal Checklist for Case Reports. RESULTS: Fifty studies involving seventy-one subjects were included. Multiple evanescent white dot syndrome (MEWDS) was the most common disease (n = 25, 35.2% %), followed by acute macular neuroretinopathy (AMN) (n = 22, 31.0%) and acute posterior multifocal placoid pigment epitheliopathy (APMPPE) (n = 4, 5.6%). They were mostly unilateral (n = 50, 70.4%). The presenting symptoms were blurred vision (n = 26, 36.6%), paracentral scotoma (n = 19, 26.8%), visual field disturbance, and photopsia (n = 7, 9.9%). The mean duration for follow-up was 10.15 ± 14.04 weeks. Nineteen subjects (29.69%) received steroids with improvement reported in 68.4%. Eleven subjects (17.19%) were managed by observation only with reported full recovery and improvement. CONCLUSION: White dot syndromes are very rare entities. Our findings highlight a possible association between COVID-19 vaccines and the occurrence of white dot syndromes. However, larger studies with good quality should be implemented to confirm these findings.

FACTORS ASSOCIATED WITH OUTCOMES OF SUPRACHOROIDAL HEMORRHAGE: An Individual Participant Data Systematic Review.

PURPOSE: To determine factors associated with visual and anatomic outcomes of suprachoroidal hemorrhage in studies published between 1990 and 2022. METHODS: Individual participant data systematic review. The protocol was prospectively registered on Open Science Framework ( https://osf.io/69v3q/ ). PubMed, EMBASE, Web of Science, and Google Scholar were searched for peer-reviewed studies of suprachoroidal hemorrhage with ≥3 patients published between January 1, 1990, and September 1, 2022. The primary outcome was the change in logarithm of the minimum angle of resolution visual acuity from the time of suprachoroidal hemorrhage diagnosis to last follow-up. RESULTS: Four hundred thirteen eyes from 49 studies were included, with mean (SD) age 60.8 (22.4) years and mean (SD) follow-up of 13.8 (12.6) months. Among 145 eyes with at least 6 months of follow-up, the mean (SD) gain in visual acuity was -0.98 (0.89) logarithm of the minimum angle of resolution. In multivariable regression, treatment with systemic steroids was associated with greater improvement in logarithm of the minimum angle of resolution visual acuity (adjusted mean [SE] -1.29 [0.09] vs. -0.16 [0.30] for no systemic steroids; P < 0.001) and greater odds of achieving anatomic success (adjusted OR 10.59, 95% confidence interval 2.59-43.3; P = 0.001). CONCLUSION: The use of systemic steroids was associated with better visual and anatomic outcomes for suprachoroidal hemorrhage.

Correlation of the macular microvasculature to the axial length in pediatric patients with high axial refractive errors.

AIMS: To compare the vascular density (VD) of the macular superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillaris (CC), and the foveal avascular zone (FAZ) among high hyperopic, high myopic, and emmetropic children using optical coherence tomography angiography (OCTA). METHODS: This was a cross sectional comparative study of otherwise healthy children with different refractive errors. Patients were recruited from Cairo University Children's Hospital. OCTA imaging was performed using the RTVue XR Avanti device with AngioVue software. Both the 3 × 3 and 6 × 6 mm macular scans were utilized. Automated measurements were obtained from the built-in machine software. Axial length (AL) measurements were done using Lenstar LS 900 optical biometer. RESULTS: Ninety eyes from 51 healthy children were included. Among high myopes, there was significant thinning of the parafovea (p < 0.001). SCP-VD was also lower in high myopes in all areas except the fovea (all p < 0.001). The DCP-VD was significantly lower in high myopes in the parafovea and perifovea. High hyperopes had lower subfoveal CC-VD. Despite high myopes showing a significantly lower OCTA signal strength, linear regression analysis revealed that AL was an independent and significant predictor for the FAZ-area, as well as parafoveal and perifoveal SCP and DCP-VD. CONCLUSION: High myopia results in a reduction of VD in both the SCP and DCP, which can be non-invasively detected and monitored using OCTA. While lower VD may, in part, be attributed to lower OCTA image quality, our findings demonstrate that AL independently and significantly predicts macular vascular parameters on OCTA in children.

Safety and Efficacy of Brolucizumab in the Treatment of Diabetic Macular Edema and Diabetic Retinopathy: A Systematic Review and Meta-Analysis.

PURPOSE: To investigate the efficacy and safety of brolucizumab in diabetic macular edema (DME) and diabetic retinopathy (DR). METHODS: In this systematic review and meta-analysis, an electronic search was done to acquire all articles describing brolucizumab use in patients with DME and DR. The review was prospectively registered on PROSPERO (CRD42022382625). Collected articles were filtered through two stages by independent reviewers. Data were extracted from the included articles and then analyzed accordingly. RESULTS: Brolucizumab induced significant improvement in best-corrected visual acuity and was either better or non-inferior to other types of anti-VEGF (MD -0.64 mu, 95% CI [-1.15, -0.13], P = .01); the same observation was noted with regards to central subfield macular thickness (CSMT) (MD -138.6 mu, 95% CI [-151.9, -125.3], P = .00001). Brolucizumab was reported to be relatively safe for use in diabetic patients, with few adverse events observed, with a higher frequency of adverse events in relation to the 3 mg dose compared to the 6 mg dose. CONCLUSION: Brolucizumab is a new drug that has potential advantages in efficacy over other anti-VEGF agents in the treatment of DME and DR. It showed significant improvement in BCVA and CSMT with the possibility of a lower dosing schedule compared to other agents. Although observed in low frequency, sight-threatening adverse effects appear to occur more frequently compared to other anti-VEGF agents. The main observed adverse event was retinal vasculitis which was seen more commonly with the 3 mg dose versus the 6 mg dose.

Recovery course of persistent posterior subretinal fluid after successful repair of rhegmatogenous retinal detachment.

PURPOSE: To investigate best corrected visual acuity (BCVA), subretinal fluid (SRF) absorption time or ellipsoid zone (EZ) restoration time and various variables in patients with persistent SRF after successful primary repair of rhegmatogenous retinal detachment (RRD). METHODS: This retrospective multicenter study allowed independent analysis of the healing pattern by two observers based on composite of serial cross-sectional macular optical coherence tomography (OCT) scans. Univariate and multivariate analyses were implemented. RESULTS: One hundred and three cases had persistent SRF after pars plana vitrectomy, scleral buckling, or pneumatic retinopexy. By univariate analysis, SRF resolution time correlated positively with the number of retinal breaks (p < 0.001) and with increased myopia (p = 0.011). Using multivariate analysis, final BCVA (log MAR) correlated positively with age, duration of RRD, initial BCVA (OR = 3.28; [95%CI = 1.44-7.47]; p = 0.015), and SRF resolution time (OR = 0.46 [95%CI 0.21-1.05]; p = 0.049). EZ restoration time was longer with increasing number of retinal tears (OR = 0.67; [95%CI 0.29-1.52]; p = 0.030), worse final BCVA, and presence of macula-off RRD (OR = 0.26; [95%CI 0.08-0.88]; p = 0.056). SRF resolution time correlated marginally with prone position. CONCLUSIONS: Residual posterior SRF is more common in eyes with multiple breaks or in myopic eyes. Final BCVA is better in younger subjects and in eyes with shorter duration of RRD. Persistent SRF is a self-limited disorder with a mean resolution of 11.2 months with good visual prognosis improving from a mean baseline logMAR of 1.08 to 0.25 at one year.

Treatment of Intermediate Uveitis-associated Retinal Vasoproliferative Tumors: A Case Series.

PURPOSE: To report the use of combination intravitreal pharmacotherapy using anti-vascular endothelial growth factor (VEGF) and short and long-term corticosteroid implants for the treatment of retinal vasoproliferative tumors (VPT) associated with intermediate uveitis. METHODS: Retrospective chart review of patients with VPT secondary to idiopathic intermediate uveitis that underwent combination intravitreal pharmacotherapy at a single center was performed. Multimodal imaging including ultrawide field color fundus photography, ultrawide field fluorescein angiography, and optical coherence tomography obtained before and after treatment were reviewed. RESULTS: Four eyes of 4 patients were treated with multiple injections of a combination of aflibercept, dexamethasone, and fluocinolone acetonide implants for VPT associated with intermediate uveitis. All 4 patients had improvement in visual acuity, intraocular inflammation, central macular thickness, and retinal vascular leakage, as well as regression of the VPT and reduction in lesion leakage on follow-up. CONCLUSION: Combination intravitreal anti-VEGF and corticosteroid implants may be a useful approach for the treatment of intermediate uveitis-associated VPTs and can lead to both functional and structural improvement.

Diabetic microaneurysms detected by fluorescein angiography spatially correlate with regions of macular ischemia delineated by optical coherence tomography angiography.

Purpose: To characterize the relationship between diabetic macular ischemia (DMI) delineated by optical coherence tomography angiography (OCTA) and microaneurysms (MAs) identified by fundus fluorescein angiography (FFA). Methods: Patients with diabetic retinopathy (DR) who underwent OCTA and FFA were retrospectively identified. FFA images were cropped and aligned with their respective OCTA images using i2k Align Retina software (Dual-Align, Clifton Park, NY, USA). Foveal avascular zone (FAZ) and ischemic areas were manually delineated on OCTA images, and MAs were marked on the corresponding FFA images before overlaying paired scans for analysis (ImageJ; National Institutes of Health, Bethesda, MD, USA). Results: Twenty-eight eyes of 20 patients were included. The average number of MAs identified in cropped FFA images was 127 ± 42. More DMI was noted in the superficial capillary plexus (SCP; 36 ± 13%) compared to the deep capillary plexus (DCP; 28 ± 14%, P < 0.001). Similarly, more MAs were associated with ischemic areas in SCP compared to DCP (92.0 ± 35.0 vs. 76.8 ± 36.5, P < 0.001). Most MAs bordered ischemic areas; fewer than 10% localized inside these regions. As DMI area increased, so did associated MAs (SCP: r = 0.695, P < 0.001; DCP: r = 0.726, P < 0.001). Density of MAs surrounding FAZ (7.7 ± 6.0 MAs/mm2) was similar to other DMI areas (SCP: 7.0 ± 4.0 MAs/mm2, P = 0.478; DCP: 9.2 ± 10.9 MAs/mm2, P = 0.394). Conclusion: MAs identified in FFA strongly associate with, and border areas of, DMI delineated by OCTA. Although more MAs are localized to SCP ischemia, the concentration of MAs associated with DCP ischemia is greater. By contrast, few MAs are present inside low-flow regions, likely because capillary loss is associated with their regression.

Visual and Anatomic Outcomes of Suprachoroidal Hemorrhage: A Systematic Review and Meta-Analysis.

TOPIC: To characterize the presentation, management, and outcomes of suprachoroidal hemorrhage (SCH). CLINICAL RELEVANCE: Suprachoroidal hemorrhage is a potentially devastating condition but there is no high-quality evidence for the prognosis or management of SCH. METHODS: We performed a systematic review and meta-analysis of peer-reviewed studies of SCH published in PubMed, EMBASE, Web of Science, or Google Scholar between January 1, 1990, and September 1, 2022. The protocol was prospectively registered on the Open Science Framework (https://osf.io/69v3q/). Random-effects models were used to calculate the pooled estimate and 95% confidence intervals (CIs) for visual acuity (VA) and anatomic outcomes. Univariable and multivariable random-effects meta-regressions were performed to determine factors associated with VA outcomes and anatomic success, defined as the retina attached at the last follow-up. RESULTS: Sixty-eight studies comprising 1246 eyes of 1245 patients were included, with mean (standard deviation [SD]) follow-up of 14.0 (9.4) months. The pooled estimate (95% CI) for mean change in logarithm of the minimum angle of resolution (logMAR) VA from baseline to the last follow-up was -0.98 (-1.22 to -0.74) (I2 = 88.4%), with 72.0% (63.5%-80.5%) (I2 = 74.3%) achieving VA improvement of ≥ 0.3 logMAR (3-line improvement in ETDRS VA), 39.6% (32.5%-46.7%) (I2 = 83.2%) achieving final VA of 1.0 logMAR (Snellen equivalent 20/200) or better, and 75.5% (68.4%-82.7%) (I2 = 74.7%) achieving anatomic success. Studies with predominantly nonspontaneous SCH and greater percent of eyes receiving systemic steroids were associated with greater improvement in logMAR VA, a greater proportion of eyes with VA improvement ≥ 0.3 logMAR, and greater proportion of eyes achieving anatomic success (all P < 0.05 univariable meta-regression). Studies with greater percent of eyes treated surgically were associated with greater proportion of eyes with VA improvement of ≥ 0.3 logMAR in (P < 0.05, univariable and multivariable analysis). The mean (SD) quality score across studies was 13.9 (2.3) out of 24, and outcomes were of very low certainty of evidence. CONCLUSION: Although limited by heterogeneous observational studies, published reports of SCH indicate that most eyes with SCH experience some degree of VA improvement and anatomic success. However, final VA outcomes remain poor, with most cases resulting in severe visual impairment or blindness. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Foldable capsular vitreous body indications, complications, and outcomes: a systematic review.

PURPOSE: Foldable capsular vitreous body (FCVB) is an emerging vitreous substitute that has been recently introduced to treat various advanced vitreoretinal conditions including severe ocular trauma, complicated retinal detachment (RD), and proliferative vitreoretinopathy. METHODS: Review protocol was prospectively registered at PROSPERO (CRD42022342310). A systematic literature search using PubMed, Ovid MEDLINE, and Google Scholar for articles published until May 2022 was performed. The search included the following keywords: foldable capsular vitreous body, FCVB, artificial vitreous substitutes, and artificial vitreous implants. Outcomes included indications of FCVB, anatomical success rates, postoperative intraocular pressure (IOP), best-corrected visual acuity (BCVA), and complications. RESULTS: A total of 17 studies that utilized FCVB up to May 2022 were included. FCVB was used intraocularly as a tamponade or extraocularly as a macular/scleral buckle for various retinal conditions including severe ocular trauma, simple and complex RD, silicone oil-dependent eyes, and highly myopic eyes with foveoschisis. FCVB was reported to be successfully implanted in the vitreous cavity of all patients. Final retinal reattachment rate ranged from 30 to 100%. Postoperative IOP improved or was maintained in most eyes, with low postoperative complication rates. Improvement in BCVA ranged from 0 to 100% of subjects. CONCLUSION: Indications of FCVB implantation have recently widened to include multiple advanced ocular conditions such as complex RD, but also include simpler conditions as uncomplicated RD. FCVB implantation showed good visual and anatomical outcomes, few IOP fluctuations, and a good safety profile. Larger comparative studies are required to further evaluate FCVB implantation.

Optic neuropathy after COVID-19 vaccination: a report of two cases.

PURPOSE: We report two cases of optic nerve pathology after the administration of the Pfizer-BioNTech and AstraZeneca-Oxford COVID-19 vaccines, respectively, and describe the implications for management of post-vaccination central nervous system (CNS) inflammation. CASE REPORTS: A 69-year-old woman presented with bilateral optic nerve head oedema, 16 days after the second dose of the Pfizer-BioNTech vaccine. She was diagnosed with post-vaccination CNS inflammatory syndrome and was treated for five days with intravenous methylprednisolone at a dose of 1 gram per day. Her optic disc swelling improved, and her vision stabilised. A 32-year-old woman presented six days after her first dose of the AstraZeneca-Oxford vaccine with two days of sudden onset of progressive blurring of vision in her left eye. Posterior segment examination revealed left optic disc swelling, and an MRI of the brain, orbit, and cervical spine was significant for left optic nerve enhancement. The patient was diagnosed with a unilateral post-vaccination optic neuritis. She was treated with a three-day course of intravenous methylprednisolone followed by oral prednisone. Her optic disc swelling and visual field improved, and she recovered 6/6 vision. CONCLUSIONS: Clinicians and patients should be aware of the potential for post-vaccination CNS inflammatory syndromes associated with COVID-19 vaccine administration. Neuroimaging and cerebrospinal fluid analysis may aid in the diagnosis of the cause of vision loss. Further studies are needed to evaluate the spectrum and frequency of optic nerve involvement associated with COVID-19 vaccination.

Regression of treatment-resistant gyrate atrophy-associated intraretinal cystic spaces using long-term diet restriction: A case report.

PURPOSE: Gyrate atrophy of the choroid and retina (GA) is a rare genetic ophthalmologic condition which primarily manifests in childhood. It is characterized by hyperornithinemia and progressive chorioretinal atrophy. Patients may develop macular intraretinal cystic spaces (ICS) for which various treatment modalities have been reported. We report a patient who failed to demonstrate visual or anatomic improvement following multiple treatments for GA-associated ICS but showed improvement following prolonged dietary modification and vitamin supplementation. CASE DESCRIPTION: A 6-year-old male patient presented with previously undiagnosed GA associated with ICS. He received 6 consecutive monthly intravitreal bevacizumab injections as well as topical nepafenac and dorzolamide for treatment of ICS without significant change detected by optical coherence tomography (OCT) following treatment. He was also maintained on an arginine restricted diet with vitamin B6 supplementation. Over the course of the ensuing year, the patient was lost to follow-up due to the coronavirus disease 2019 pandemic. When he returned, his vision was stable, and OCT showed regression of the ICS. His mother reported that he had continued only on dietary restriction and vitamin B6 supplementation with no other medications or interventions. Plasma ornithine level measurement confirmed dietary compliance. Further follow-up showed continued stabilization of the condition. CONCLUSION: In addition to retarding progressive chorioretinal atrophy, prolonged dietary modifications may result in improvement of treatment-resistant GA-associated ICS. Parents' education on the value of dietary modifications for patients with GA is highly recommended.

UTILITY OF OCULAR ß- d -GLUCAN TESTING IN PATIENTS WITH FUNGAL ENDOPHTHALMITIS.

PURPOSE: To assess the diagnostic utility of (1→3)-ß- d -glucan (BDG) in ocular fluid of patients with fungal endophthalmitis. METHODS: This prospective pilot single-center study evaluated aqueous and vitreous humor BDG levels of suspected fungal endophthalmitis, bacterial endophthalmitis, and noninfectious controls with the standard Fungitell assay and the Fungitell STAT assay. ß- d -Glucan levels were compared using generalized linear models followed by post hoc pairwise comparisons. RESULTS: Seven fungal endophthalmitis, 6 bacterial endophthalmitis, and 17 noninfectious ocular samples were evaluated. Mean aqueous BDG concentrations were 204, 11.0, and 9.6 pg/mL for fungal endophthalmitis, bacterial endophthalmitis, and noninfectious controls, respectively ( P = 0.01, fungal vs. bacterial; P = 0.0005, fungal vs. noninfectious controls). Mean vitreous BDG concentrations were 165, 30.3, and 5.4 pg/mL, respectively ( P = 0.001 for fungal vs. bacterial; P < 0.0001 for fungal vs. noninfectious controls). Mean vitreous BDG index (Fungitell STAT) values were 1.7, 0.4, and 0.3, respectively ( P = 0.001, fungal vs. bacterial; P = 0.0004, fungal vs. noninfectious controls). The Pearson correlation between BDG levels and BDG index was high (correlation coefficient = 0.99, P < 0.001). CONCLUSION: Significantly elevated ocular BDG levels were found in fungal endophthalmitis compared with bacterial endophthalmitis and noninfectious controls. Our study suggests a potential utility for BDG testing in the diagnosis of fungal endophthalmitis, and a larger study is warranted.

Persistent diabetic macular edema: Definition, incidence, biomarkers, and treatment methods.

Intravitreal antivascular endothelial growth factor (anti-VEGF) treatment has drastically improved the visual and anatomical outcomes in patients with diabetic macular edema (DME); however, success is not always guaranteed, and a proportion of these eyes demonstrate persistent DME (pDME) despite intensive treatment. While standardized criteria to define these treatment-resistant eyes have not yet been established, many studies refer to eyes with no clinical response or an unsatisfactory partial response as having pDME. A patient is considered to have pDME if the retinal thickness improves less than 10-25% after 6 months of treatment. A range of treatment options have been recommended for eyes with pDME, including switching anti-VEGF agents, using corticosteroids and/or antioxidant drugs in adjunct with anti-VEGF therapy, and vitrectomy. In addition, multimodal imaging of DME eyes may be advantageous in predicting the responsiveness to treatment; this is beneficial when initiating alternative therapies. We explore the literature on persistent DME regarding its defining criteria, incidence, the baseline biological markers that may be useful in anticipating the response to treatment, and the available treatment options.

Ocular Vascular Events following COVID-19 Vaccines: A Systematic Review.

The main aim of this study is to investigate the current evidence regarding the association between COVID-19 vaccination and ocular vascular events. The protocol is registered on PROSPERO (CRD42022358133). On 18 August 2022, an electronic search was conducted through five databases. All original articles reporting individuals who were vaccinated with COVID-19 vaccines and developed ophthalmic vascular events were included. The methodological quality of the included studies was assessed using the NIH tool. A total of 49 studies with 130 ocular vascular cases were included. Venous occlusive events were the most common events (54.3%), which mostly occurred following the first dose (46.2%) and within the first five days following vaccination (46.2%). Vascular events occurred more with the Pfizer and AstraZeneca vaccines (81.6%), and mostly presented unilaterally (73.8%). The most frequently reported treatment was intravitreal anti-VEGF (n = 39, 30.4%). The majority of patients (90.1%) demonstrated either improvement (p = 0.321) or persistence (p = 0.414) in the final BCVA. Ophthalmic vascular events are serious vision-threatening side effects that have been associated with COVID-19 vaccination. Clinicians should be aware of the possible association between COVID-19 vaccines and ocular vascular events to provide early diagnosis and treatment.

COVID-19 Vaccine-Associated Optic Neuropathy: A Systematic Review of 45 Patients.

We provide a systematic review of published cases of optic neuropathy following COVID-19 vaccination. We used Ovid MEDLINE, PubMed, and Google Scholar. Search terms included: "COVID-19 vaccination", "optic neuropathy", "optic neuritis", and "ischemic optic neuropathy". The titles and abstracts were screened, then the full texts were reviewed. Sixty eyes from forty-five patients (28 females) were included. Eighteen eyes from fourteen patients (31.1%) were diagnosed with anterior ischemic optic neuropathy (AION), while 34 eyes from 26 patients (57.8%) were diagnosed with optic neuritis (ON). Other conditions included autoimmune optic neuropathy and Leber hereditary optic neuropathy. Fifteen patients (33.3%) had bilateral involvement. The mean age of all patients was 47.4 ± 17.1 years. The mean age of AION patients was 62.9 ± 12.2 years and of ON patients was 39.7 ± 12.8 years (p < 0.001). The mean time from vaccination to ophthalmic symptoms was 9.6 ± 8.7 days. The mean presenting visual acuity (VA) was logMAR 0.990 ± 0.924. For 41 eyes with available follow-up, the mean presenting VA was logMAR 0.842 ± 0.885, which improved to logMAR 0.523 ± 0.860 at final follow-up (p < 0.001). COVID-19 vaccination may be associated with different forms of optic neuropathy. Patients diagnosed with ON were more likely to be younger and to experience visual improvement. More studies are needed to further characterize optic neuropathies associated with COVID-19 vaccination.