Corrigendum: Comparison of indocyanine green angiography and swept-source wide-field optical coherence tomography angiography in posterior uveitis.

[This corrects the article DOI: 10.3389/fmed.2022.853315.].

Gender differences in retinal diseases: A review.

Gender medicine is a medical specialty that addresses gender differences in health and disease. Traditionally, medical research and clinical practice have often been focused on male subjects and patients. As a result, gender differences in medicine have been overlooked. Gender medicine considers the biological, psychological, and social differences between the genders and how these differences affect the development, diagnosis, treatment, and prevention of disease. For ophthalmological diseases epidemiological differences are known. However, there are not yet any gender-based ophthalmic treatment approaches for women and men. This review provides an overview of gender differences in retinal diseases. It is intended to make ophthalmologists, especially retinologists, more sensitive to the topic of gender medicine. The goal is to enhance comprehension of these aspects by highlighting fundamental gender differences. Integrating gender medicine into ophthalmological practice helps promote personalized and gender-responsive health care and makes medical research more accurate and relevant to the entire population.

Assessment of choriocapillaris and choroidal vascular changes in posterior uveitis using swept-source wide-field optical coherence tomography angiography.

PURPOSE: To evaluate choriocapillaris (CC) and choroidal vascular changes in patients with posterior uveitis using swept-source (SS) wide-field optical coherence tomography angiography (OCTA). METHOD: Consecutive patients with posterior uveitis were evaluated using 3×3 mm and 12×12 mm OCTA scan patterns and montage images of 5×12×12 mm or 2×15×9 mm, covering approximately 70°-90° of the retina. The images were quantitatively and qualitatively analysed and compared with healthy controls. RESULTS: Eighty-six eyes of 56 patients with posterior uveitis (mean age 45.2±19.9 years; 58.9% female), and 38 eyes of 19 age-matched healthy controls (57.9% female) were included. The mean perfusion density (PD) in 3×3 mm and 12×12 mm CC scans was significantly lower in eyes with posterior uveitis compared with those of healthy controls. However, no significant difference in the mean PD of choroidal scans was found comparing eyes with posterior uveitis and healthy controls. The mean PD in eyes with active disease was significantly higher compared with the inactive eyes on 12×12 mm choroidal scans (55.61% vs 51.25%, p=0.02), while no difference was found in the CC slabs. CONCLUSION: CC and choroidal assessment using OCTA provides useful information in patients with posterior uveitis. SS-OCTA metrics of the CC and choroidal slabs are promising tools in uveitis patients in the future. TRIAL REGISTRATION NUMBER: NCT02811536.

LIGHTSITE III: 13-Month Efficacy and Safety Evaluation of Multiwavelength Photobiomodulation in Nonexudative (Dry) Age-Related Macular Degeneration Using the Lumithera Valeda Light Delivery System.

PURPOSE: The LIGHTSITE III study evaluated multiwavelength photobiomodulation (PBM) therapy in nonexudative (dry) age-related macular degeneration (AMD) using the LumiThera Valeda Light Delivery System. METHODS: LIGHTSITE III is a randomized, controlled trial to assess the safety and effectiveness of PBM in dry AMD. Subjects were given multiwavelength PBM (590, 660, and 850 nm) or Sham treatment delivered in a series of nine sessions over 3 to 5 weeks every four months over 24 months. Subjects were assessed for efficacy and safety outcomes. Data from the 13-month analysis are presented in this report. RESULTS: A total of 100 subjects (148 eyes) with dry AMD were randomized. LIGHTSITE III met the primary efficacy best-corrected visual acuity endpoint with a significant difference between PBM (n = 91 eyes) and Sham (n = 54 eyes) groups (Between group difference: 2.4 letters (SE 1.15), CI: -4.7 to -0.1, P = 0.02) (PBM alone: 5.4 letters (SE 0.96), CI: 3.5 to 7.3, P < 0.0001; Sham alone: 3.0 letters (SE 1.13), CI: 0.7-5.2, P < 0.0001). The PBM group showed a significant decrease in new onset geographic atrophy ( P = 0.024, Fisher exact test, odds ratio 9.4). A favorable safety profile was observed. CONCLUSION: LIGHTSITE III provides a prospective, randomized, controlled trial showing improved clinical and anatomical outcomes in intermediate dry AMD following PBM therapy.

The Humira in Ocular Inflammations Taper (HOT) Study.

PURPOSE: To assess factors that impact the risk of relapse in patients with noninfectious uveitis (NIU) who undergo adalimumab tapering after achieving remission. DESIGN: Retrospective study. METHODS: In this multicenter study, patients with NIU were treated with adalimumab and subsequently tapered. Patient demographics, type of NIU, onset and duration of disease, the period of inactivity before tapering adalimumab, and the tapering schedule were collected. The primary outcome measures were independent predictors of the rate of uveitis recurrence after adalimumab tapering. RESULTS: Three hundred twenty-eight patients were included (54.6% female) with a mean age of 34.3 years. The mean time between disease onset and initiation of adalimumab therapy was 35.2 ± 70.1 weeks. Adalimumab tapering was commenced after a mean of 100.8 ± 69.7 weeks of inactivity. Recurrence was observed in 39.6% of patients at a mean of 44.7 ± 61.7 weeks. Patients who experienced recurrence were significantly younger than those without recurrence (mean 29.4 years vs 37.5 years, P = .0005), and the rate of recurrence was significantly higher in younger subjects (hazard ratio [HR] = 0.88 per decade of increasing age, P = .01). The lowest rate of recurrence was among Asian subjects. A faster adalimumab taper was associated with an increased recurrence rate (HR = 1.23 per unit increase in speed, P < .0005). Conversely, a more extended period of remission before tapering was associated with a lower rate of recurrence (HR = 0.97 per 10-weeks longer period of inactivity, P = .04). CONCLUSIONS: When tapering adalimumab, factors that should be considered include patient age, race, and duration of disease remission on adalimumab. A slow tapering schedule is advisable.

RETINAL TECTONICS AFTER MACULAR PUCKER SURGERY: Thickness Changes and En Face Displacement Recovery.

PURPOSE: To study visual function, retinal layer thickness changes, and tangential displacement after pars plana vitrectomy for epiretinal membrane. METHODS: Retrospective series of patients undergoing pars plana vitrectomy for epiretinal membrane, with 6-month follow-up including best-corrected visual acuity, optical coherence tomography, M-charts, epiretinal membrane grading, and infrared fundus photograph at time 0 (T0, preop) at months 1 (T1), 3 (T3), and 6 (T6) postop (±1 week). Retinal layer thickness and tangential ( en face ) retinal displacement between successive times for the entire retinal surface and the central horizontal and vertical meridian were also measured. En face displacement was calculated as optical flow of consecutive images. RESULTS: Average best-corrected visual acuity improved from 0.28 ± 0.08 logarithm of Minimum Angle of Resolution at T0 to 0.16 ± 0.25 at T6 ( P = 0.05), best-corrected visual acuity improvement correlated with best corrected visual acuity (BCVA) at T0 ( P < 0.001). Vertical metamorphopsia decreased from 1.33° ± 0.70° at T0 to 0.82° ± 0.69° at T6 ( P < 0.05). Foveal thickness reduced from 453 ± 53 µ m at T0 to 359 ± 31 µ m at T6 ( P < 0.05) and reduction correlated with best-corrected visual acuity improvement ( P < 0.05). Foveal layers decreased ( P < 0.05) in all cases. The mean en face deformation was 155.82 ± 50.17 µ m and mostly occurred in the first month: T0-T1 displacement was 83.59 ± 30.28 µ m, T1-T3 was 36.28 ± 14.45 µ m, while T3-T6 was 39.11 ± 22.79 µ m ( P < 0.001) on average. Perifoveal and parafoveal deformation correlated with optical coherence tomography foveal thickness reduction at all time intervals (1, 3, and 6 months: P < 0.01). CONCLUSION: Epiretinal membrane peeling affects all retinal layer thickness and results in new force balance across the entire retina and tangential displacement. Both en face and in-depth changes correlate with visual function.

How the immune response to the structural proteins of SARS-CoV-2 affects the retinal vascular endothelial cells: an immune thrombotic and/or endotheliopathy process with in silico modeling.

Thrombotic events associated with SARS-CoV-2 at the vascular endothelium still remains unclear. The aim of the current study is to determine the relationship between cellular proteins on the (ocular) vascular endothelial surface and the immune thrombotic and/or endotheliopathy process elicited by SARS-CoV-2 using an in-silico modeling. The structural S (spike glycoprotein), N (nucleocapsid protein), M (membrane protein), and E (envelope protein) proteins, an accessory protein (ORF1ab) of SARS-CoV-2 and 158 cellular proteins associated with retinal vascular endothelial cell surface or structure were included in this study for comparison of three-dimensional (3D) structure and sequence. Sixty-nine of the retinal proteins were obtained from the Uniprot database. Remaining proteins not included in the database were included in the study after they were converted into 3D structures using the RaptorX web tool. Sequence and three-dimensional structure of SARS-COV-2 S, N, M, E, ORF1ab proteins and retinal vascular endothelial proteins were compared with mTM-align server. Proteins with significant similarity (score above 0.5) were validated with the TM-align web server. Immune and thrombosis-related protein-receptor interactions of similar proteins was checked with CABS-dock. We detected a high level of structural similarity between E protein and ACE, ACE2, LAT1, and TM9SF4 endothelial proteins. In addition, PECAM-1 was found to be structurally similar to ORF1ab and S protein. When we evaluated the likelihood/potential to stimulate an immune responses/a cytokine release, TLR-2 and TLR-3, which are highly susceptible to SARS-CoV2, showed a potential receptor-protein interaction with retinal vascular endothelial proteins. Our study demonstrates that SARS-CoV-2 proteins may have structural similarities with vascular endothelial proteins, and therefore, as immunological target sites, the counterpart proteins on the endothelial surface of many organs may also be secondarily affected by any immune response against SARS-CoV-2 structural proteins.

MULTIPLE EVANESCENT WHITE DOT SYNDROME FROM A PATIENT'S PERSPECTIVE.

PURPOSE: Multiple evanescent white dot syndrome is a self-limiting inflammatory condition of the outer retina. Only little information is available how patients experience their symptoms. METHOD: We report a case of a 28-year-old male graphic designer with multiple evanescent white dot syndrome, who precisely illustrated the development and course of the characteristic symptoms while looking at the ceiling, at a face and on his phone. RESULT: At onset, the scotoma was sparking/shiny and appeared on the temporal field of view, consistent with an enlarged blind spot. Over the course of the disease, the scotoma decreased in intensity and moved superiorly and nasally until it completely faded. CONCLUSION: Illustrations from a patient's perspective over the course of the disease can be beneficial for physicians and other multiple evanescent white dot syndrome patients for a better understanding and monitoring of their disease.

Non-Invasive Treatment of Early Diabetic Macular Edema by Multiwavelength Photobiomodulation with the Valeda Light Delivery System.

Purpose: Diabetes is associated with ocular complications including diabetic macular edema (DME). Current therapies are invasive and include repeated intravitreal injections and laser therapy. Photobiomodulation (PBM) is a treatment (Tx) that utilizes selected wavelengths of light to induce cellular benefits including reduction of inflammation and edema. This single-center, open-label, post-hoc analysis explored the utility of multiwavelength PBM in subjects with DME. Methods: Analysis included review of data from patients undergoing standard clinical care with an approved and marketed PBM medical device, the Valeda® Light Delivery System. Subjects with early-stage DME with good vision (Best-corrected visual acuity (BCVA) > 20/25, logMAR > 0.1) were evaluated in clinic and treated with one series of multiwavelength PBM (Tx delivered 3x/week over 3-4 weeks; total of 9 Tx sessions). Clinical, anatomical, and safety parameters were assessed in addition to subjective quality of life. Results: A total of 30 eyes (19 subjects) were analyzed. Subjects were predominately male (68.4%) with a mean age of 56 ± 14 years. Reductions in central retinal thickness (CRT), resolution of intraretinal fluid (IRF) and improvement in diabetic retinopathy severity scale scores were observed following PBM treatment in select patients. Baseline BCVA remained stable over the follow-up observation period of 3 months post-PBM. Approximately 64% of patients reported subjective improvements in their ocular condition and decreased influence in everyday life. Detailed OCT evaluations confirmed no safety issues related to phototoxicity up to 16 months. Conclusion: Early-stage DME subjects treated with Valeda multiwavelength PBM showed improvements in clinical and anatomical parameters. The Valeda multiwavelength PBM approach demonstrates a favorable safety profile with no signs of phototoxicity following an independent OCT review. PBM therapy may offer an alternative, non-invasive treatment strategy with a unique mechanism and modality for patients with early-stage DME.

Expression of key SARS-CoV-2 entry molecules in surgically obtained human retinal biopsies.

PURPOSE: To investigate the presence of ACE2, TMPRSS2 and Furin, i.e., a key player in the ocular infection with SARS-COV-2, in surgically obtained human retinal tissue samples from SARS-CoV-2-negative patients, using gene expression analysis. METHODS: The mechanisms and entry paths of ocular infections have been ill-defined so far. To better understand the possible entry routes, we used surgically explanted retinal tissue from nine patients that were not infected with SARS-CoV-2 and analyzed the message expression of the three key molecules that confer viral entry into cells using polymerase chain reaction. RESULTS: The median age of the patients (n = 9) included in the study was 52 years (IQR 48, 55). Eight patients underwent surgery for rhegmatogenous retinal detachment and one patient for tractional retinal detachment. Gene expression for the proteins studied was detected in all nine patients. The results of analysis by Livak's method (2001) demonstrated a median TMPRSS2 gene expression value of 20.9 (IQR 11.7, 33.7), a median ACE2 gene expression value of 2.09 (IQR 1.14, 2.79) and a median Furin gene expression value of 8.33 (IQR 5.90, 11.8). CONCLUSION: In conclusion, TMPRSS2, Furin and ACE2 are expressed in the retina and may contribute to the retinal involvement in COVID-19 patients. Expression may vary among individuals, which may explain why some patients may be more prone to retinal involvement during SARS-CoV-2 infection COVID-19 patients than others. Variability in the expression of TMPRSS2, Furin and ACE2 proteins themselves may also explain the presence or development of retinal symptoms of varying severity.

Herpetic anterior uveitis following COVID-19 vaccines: a case series.

Purpose: To report a case series of herpetic uveitis following COVID-19 vaccinations. Methods: Demographic, clinical and treatment-related data of herpetic anterior uveitis cases was collected at five tertiary eye hospitals between January 2021 and June 2022. A retrospective database review at one of the centers comparing the number of cases of herpetic eye disease before and after the introduction of COVID-19 vaccination was performed as well. Results: Twenty-four patients (9 female, 15 male) with a mean age of 54 years (range 28-83 years) were diagnosed with herpetic uveitis, reporting an onset of symptoms 3-42 days after the first, second or third dose of COVID-19 vaccination. Median time between vaccination and onset of herpetic eye disease was 10 days (mean 12.7 ± 10.15 days) days. The administered vaccines were BNT162b2, mRNA-1273, BBIBP-CorV and Ad26.COV2.S. The cases included 11 HSV, 10 VZV and 1 CMV anterior uveitis, 2 were not further specified. There was an equal number of first episodes (n = 12, 50%) and recurrent episodes (n = 12, 50%). Response to established regimens was generally good. The retrospective database review revealed the exact same incidence of herpetic uveitis during the pandemic and ongoing vaccination compared to prior SARS-CoV-2. Conclusion: This report includes 24 cases of herpetic anterior uveitis in a temporal relationship to various COVID-19 vaccines. This study supports the potential risk of herpetic eye disease following COVID-19 vaccines, but proof of a direct, causal relationship is missing.

Optical coherence tomography angiography in diabetic retinopathy.

There remain many unanswered questions on how to assess and treat the pathology and complications that arise from diabetic retinopathy (DR). Optical coherence tomography angiography (OCTA) is a novel and non-invasive three-dimensional imaging method that can visualize capillaries in all retinal layers. Numerous studies have confirmed that OCTA can identify early evidence of microvascular changes and provide quantitative assessment of the extent of diseases such as DR and its complications. A number of informative OCTA metrics could be used to assess DR in clinical trials, including measurements of the foveal avascular zone (FAZ; area, acircularity, 3D para-FAZ vessel density), vessel density, extrafoveal avascular zones, and neovascularization. Assessing patients with DR using a full-retinal slab OCTA image can limit segmentation errors and confounding factors such as those related to center-involved diabetic macular edema. Given emerging data suggesting the importance of the peripheral retinal vasculature in assessing and predicting DR progression, wide-field OCTA imaging should also be used. Finally, the use of automated methods and algorithms for OCTA image analysis, such as those that can distinguish between areas of true and false signals, reconstruct images, and produce quantitative metrics, such as FAZ area, will greatly improve the efficiency and standardization of results between studies. Most importantly, clinical trial protocols should account for the relatively high frequency of poor-quality data related to sub-optimal imaging conditions in DR and should incorporate time for assessing OCTA image quality and re-imaging patients where necessary.

Multimodal Imaging Study of Patients With Vitamin A Deficiency Retinopathy.

OBJECTIVES: To describe multimodal imaging findings of vitamin A deficiency retinopathy. METHODS: A retrospective study of patients with serum retinol < 0.3 mg/L. Fundus color photos, spectral domain-optical coherence tomography (SD-OCT), and fundus autofluorescence (FAF) were reviewed and, when available, electrophysiological tests were analyzed. RESULTS: Forty-five eyes (63.9 ± 15.7 years) were included. Ultra-widefield fundus photography showed drusen-like deposits (53.3%) and macular retinal pigment epithelium (RPE) mottling (40%). The deposits were hypoautofluorescent, and a perifoveal hyperautofluorescent ring was present in 8.9%. By SD-OCT, the ellipsoid zone had an irregular appearance (100%) and conical deposits anterior to the RPE (33.3%). Electroretinogram (ERG) (66.7%) showed a decrease in b-wave in the scotopic registers, and microperimetry (4.4%) showed decreased foveal sensitivity. After vitamin A supplementation, SD-OCT and FAF showed resolution of all findings. Forty percent of eyes had restoration of the scotopic registers in ERG and improved macular sensitivity by microperimetry (4.4%). CONCLUSIONS: Vitamin A deficiency causes a mild cone dysfunction in addition to the more severe absent rod response. [Ophthalmic Surg Lasers Imaging Retina 2023;54:330-336.].

Faricimab for the Treatment of Diabetic Macular Edema and Neovascular Age-Related Macular Degeneration.

Nowadays; intravitreal anti-vascular endothelial growth factor (VEGF) drugs are considered the first-line therapeutic strategy for treating macular exudative diseases; including wet age-related macular degeneration (w-AMD) and diabetic macular edema (DME). Despite the important clinical achievements obtained by anti-VEGF drugs in the management of w-AMD and DME; some limits still remain; including high treatment burden; the presence of unsatisfactory results in a certain percentage of patients and long-term visual acuity decline due to complications such as macular atrophy and fibrosis. Targeting the angiopoietin/Tie (Ang/Tie) pathway beyond the VEGF pathway may be a possible therapeutic strategy; which may has the potential to solve some of the previous mentioned challenges. Faricimab is a new; bispecific antibody targeting both VEGF-A and the Ang-Tie/pathway. It was approved by FDA and; more recently; by EMA for treating w-AMD and DME. Results from phase III trials TENAYA and LUCERNE (w-AMD) and RHINE and YOSEMITE (DME) have shown the potential of faricimab to maintain clinical efficacy with more prolonged treatment regimens compared to aflibercept (12 or 16 weeks) with a a good safety profile.

Imaging in retinal vascular disease: A review.

Retinal vascular diseases represent a broad field of ocular pathologies. Retinal imaging is an important tool for diagnosis, prognosis and follow up of retinal vascular diseases. It includes a wide variety of imaging techniques ranging from colour fundus photography and optical coherence tomography to dynamic diagnostic options such as fluorescein angiography, and optical coherence tomography angiography. The newest developments in respective imaging techniques include widefield imaging to assess the retinal periphery, which is of especial interest in retinal vascular diseases. Automatic image analysis and artificial intelligence may support the image analysis and may prove valuable for prognostic purposes. This review provides a broad overview of the imaging techniques that have been used in the past, today and maybe in the future to stage and monitor retinal vascular disease with focus on the main disease entities including diabetic retinopathy, retinal vein occlusion, and retinal artery occlusion.

LIGHTSITE II Randomized Multicenter Trial: Evaluation of Multiwavelength Photobiomodulation in Non-exudative Age-Related Macular Degeneration.

INTRODUCTION: Photobiomodulation (PBM) represents a potential treatment for non-exudative age-related macular degeneration (AMD). PBM uses wavelengths of light to target components of the mitochondrial respiratory chain to improve cellular bioenergetic outputs. The aim of this study was to further investigate the effects of PBM on clinical, quality of life (QoL) and anatomical outcomes in subjects with intermediate stage non-exudative AMD. METHODS: The multicenter LIGHTSITE II study was a randomized clinical trial evaluating safety and efficacy of PBM in intermediate non-exudative AMD. The LumiThera Valeda® Light Delivery System delivered multiwavelength PBM (590, 660 and 850 nm) or sham treatment 3 × per week over 3-4 weeks (9 treatments per series) with repeated treatments at baseline (BL), 4 and 8 months. Subjects were enrolled with 20/32 to 20/100 best-corrected visual acuity (BCVA) and no central geographic atrophy (GA) within the central fovea (500 µm). RESULTS: LIGHTSITE II enrolled 44 non-exudative AMD subjects (53 eyes). PBM-treated eyes showed statistically significant improvement in BCVA at 9 months (n = 32 eyes, p = 0.02) with a 4-letter gain in the PBM-treated group versus a 0.5-letter gain in the sham-treated group (ns, p < 0.1) for patients that received all 27 PBM treatments (n = 29 eyes). Approximately 35.3% of PBM-treated eyes showed ≥ 5-letter improvement at 9 months. Macular drusen volume was not increased over time in the PBM-treated group but did show increases in the sham-treated group. While PBM and sham groups both showed GA lesion growth in the trial period, there was 20% less growth in the PBM group over 10 months, suggesting potential disease-modifying effects. No safety concerns or signs of phototoxicity were observed. CONCLUSION: These results confirm previous clinical testing of multiwavelength PBM and support treatment with Valeda as a novel therapy with a unique mechanism of action as a potential treatment for non-exudative AMD. TRIAL REGISTRATION: Clinicaltrial.Gov Registration Identifier: NCT03878420.

Transforming ophthalmology in the digital century-new care models with added value for patients.

Ophthalmology faces many challenges in providing effective and meaningful eye care to an ever-increasing group of people. Even health systems that have so far been able to cope with the quantitative patient increase, due to their funding and the availability of highly qualified professionals, and improvements in practice routine efficiency, will be pushed to their limits. Further pressure on care will also be caused by new active substances for the largest group of patients with AMD, the so-called dry form. Treatment availability for this so far untreated group will increase the volume of patients 2-3 times. Without the adaptation of the care structures, this quantitative and qualitative expansion in therapy will inevitably lead to an undersupply.There is increasing scientific evidence that significant efficiency gains in the care of chronic diseases can be achieved through better networking of stakeholders in the healthcare system and greater patient involvement. Digitalization can make an important contribution here. Many technological solutions have been developed in recent years and the time is now ready to exploit this potential. The exceptional setting during the SARS-CoV-2 pandemic has shown many that new technology is available safely, quickly, and effectively. The emergency has catalyzed innovation processes and shown for post-pandemic time after that we are equipped to tackle the challenges in ophthalmic healthcare - ultimately for the benefit of patients and society.

Experts Opinion: OCTA vs. FFA/ICG in Uveitis - Which Will Survive?

Will optical coherence tomography angiography (OCTA) replace invasive imaging techniques like fundus fluorescein angiography (FFA) and indocyanine green (ICG) angiography entirely? While OCTA is being increasingly applied in the field of medical retina, will we see this change in the subspeciality of uveitis? In this article, five uveitis specialists with renowned imaging expertise answer to 10 specific questions to address this issue. The final verdict based on the comments of the experts suggests that FFA and ICG cannot be replaced by OCTA in uveitis, at least for now. While OCTA can offer new insights into the pathogenesis of certain inflammatory conditions and help in the diagnosis of complications like inflammatory choroidal neovascularisation, multimodal imaging is still the preferred approach in the assessment of patients with uveitis.

Topical treatment of diabetic macular edema using dexamethasone ophthalmic suspension: A randomized, double-masked, vehicle-controlled study.

PURPOSE: To evaluate topical dexamethasone ophthalmic suspension OCS-01 (Oculis SA, Lausanne, Switzerland) in diabetic macular edema (DME). METHODS: This was a multicenter, double-masked, parallel-group, randomized, Phase 2 study. Patients aged 18-85 years with DME of <3 years duration, ETDRS central subfield thickness ≥ 310 µm by SD-OCT, and ETDRS letter score ≤ 73 and ≥ 24 in the study eye were randomized 2:1 to OCS-01 or matching vehicle, 1 drop 3 times/day for 12 weeks. Efficacy was evaluated as change from baseline to Week 12 of ETDRS letter score and central macular thickness (CMT). The primary analysis used a linear model with baseline ETDRS letters as a covariate, and missing data imputed using multiple imputation pattern mixture model techniques. Active treatment was considered superior to vehicle if the one-sided p-value was <0.15 and the difference in mean change from baseline in ETDRS letters was >0. RESULTS: Mean CMT showed a greater decrease from baseline with OCS-01 (N = 99) than vehicle (N = 45) at Week 12 (-53.6 vs -16.8 µm, p = 0.0115), with significant differences favouring OCS-01 from Weeks 2 to 12. OCS-01 was well-tolerated, and increased intraocular pressure was the most common adverse event. Mean change in ETDRS letter score from baseline to Week 12 met the p was +2.6 letters with topical OCS-01 and 1 letter with vehicle (p = 0.125). In a post-hoc analysis, there was a greater difference in patients with baseline BCVA ≤65 letters, the OCS-01 group improved 3.8 letters compared with 0.9 letters with vehicle. CONCLUSION: Topical OCS-01 was significantly more effective than vehicle in improving central macular thickness in patients with DME. Visual improvement was better in eyes with lower baseline vision.