Effects of Perfluorocarbon Use during Rhegmatogenous Retinal Detachment Surgery on Postoperative Outcomes.

INTRODUCTION: The aim of this study was to determine whether the use of perfluorocarbon liquid (PFCL) affects the rate of retinal re-attachments after an initial attachment by vitrectomy in eyes with rhegmatogenous retinal detachment (RRD). METHODS: This was a retrospective, observational, multicenter study of 3,446 eyes registered in the Japanese vitreoretinal surgery treatment information database. Of these, 2,648 eyes had undergone vitrectomy as the first surgery for RRD. The re-attachment rates after the primary vitrectomy with or without PFCL were evaluated. In addition, the significance of factors affecting the re-detachments was determined by univariate and multivariate analyses. The measured outcomes were the rates of re-attachments after the primary vitrectomy with or without the use of PFCL. RESULTS: A total of 2,362 eyes in the database were analyzed: 325 had and 2,037 did not have PFCL injected into the vitreous cavity during the vitrectomy. The rate of re-attachments was 91.5% in the PFCL group and 93.2% in the non-PFCL group (p = 0.46, χ2 test). Although there were several risk factors associated with the re-detachments in eyes without PFCL (p < 0.05, Welch's t tests, and Fisher's exact tests), they were not associated in eyes with PFCL use. However, multivariate analyses showed that there was no significant association between the use and the non-use of PFCL in the rate of re-detachments (ß = -0.08, p = 0.46). CONCLUSIONS: The use of PFCL during the initial vitrectomy for RRD does not affect the rate of re-attachments.

Effects of Topical or Intravitreal Application of Anti-Vascular Endothelial Growth Factor on Density of Intestinal Blood Vessels of Mice.

Background and Objectives: Anti-vascular endothelial growth factor (anti-VEGF) therapy has become the first-line treatment for diabetic macular edema. However, it is still not clear whether anti-VEGF agents act on systemic blood vessels. The aim of this study is to determine whether a direct topical application or intravitreal injection of anti-VEGF will change the intestinal blood vessels of mice. Materials and Methods: C57BL/6 mice were laparotomied under deep anesthesia, and the blood vessels on the surface of the intestines were exposed, examined, and photographed through a dissecting microscope. Vascular changes were evaluated before and at 1, 5, and 15 min after the topical application of 50 µL of the different anti-VEGF agents onto the surface of the intestine (group S) or after the intravitreal injection (group V). The vascular density (VD) was determined for five mice in each group before and after 40 µg/µL of aflibercept (Af), or 25 µg/µL of bevacizumab (Be), or 10 µg/µL of ranibizumab (Ra) were applied. Endothelin-1 (ET1), a potent vasoconstrictor, was used as a positive control, and phosphate-buffered saline (PBS) was used as a control. Results: For group S, no significant changes were observed after PBS (baseline, 1, 5, and 15 min: 46.3, 44.5, 44.8, and 43.2%), Be (46.1, 46.7, 46.7, and 46.3%), Ra (44.7, 45.0, 44.7, and 45.6%), and Af (46.5, 46.2, 45.9, and 46.1%, repeated ANOVA) were applied topically. Significant decreases in the VD were observed after ET1 (46.7, 28.1, 32.1, and 34.0%, p < 0.05) was topically applied. For group V, no significant differences were observed for all anti-VEGF agents. Conclusions: The topical application or intravitreal injections of anti-VEGF agents do not cause a change in the VD of the intestinal vessels, which may be related to its safety.

Intravitreal aflibercept for diabetic macular edema in real-world clinical practice in Japan: 24-month outcomes.

PURPOSE: To report the safety and effectiveness of intravitreal aflibercept (IVT-AFL) for diabetic macular edema (DME) in the real-world clinical practice setting in Japan. METHODS: In this prospective, multicenter, observational, post-marketing surveillance, patients with DME newly receiving IVT-AFL were enrolled. During a 24-month follow-up, the primary outcome was the occurrence of safety events. Other pre-specified endpoints were effectiveness indicators, such as best-corrected visual acuity (BCVA), central retinal thickness, and injection frequency. RESULTS: In total, 646 patients administered at least one IVT-AFL injection were included in the safety analysis. During the follow-up period, adverse events occurred in 42 patients (6.50%), whereas adverse drug reactions occurred in 12 (1.86%). In the 12 patients who had adverse drug reactions, seven events occurred in seven patients within the first month of the most recent injection. In addition, 622 patients were included in the effectiveness analysis set. The number of injections over 24 months was 3.6 ± 3.0 (mean ± standard deviation [SD]). BCVA (logarithm of the minimum angle of resolution) was 0.437 ± 0.362 (mean ± SD) (n = 622) at baseline and 0.321 ± 0.348 (n = 177) after 24 months of treatment with IVT-AFL. Central retinal thickness was 440.8 ± 134.2 µm (mean ± SD) (n = 444) at baseline and 355.5 ± 126.4 µm (n = 140) at 24 months. CONCLUSION: Routine administration of IVT-AFL for DME was not associated with new safety concerns, and BCVA outcomes were maintained over 24 months in the real-world setting. Nonetheless, patients in this real-world setting received fewer injections than those in clinical trials, suggesting that a margin for improvement exists in clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02425501.

Effects of suspension of anti-vascular endothelial growth factor treatment for neovascular age-related macular degeneration in clinical setting.

PURPOSE: To investigate the outcomes of a suspension of anti-vascular endothelial growth factor (anti-VEGF) treatments in the eyes with neovascular age-related macular degeneration (nAMD). METHODS: This was a retrospective study that examined eyes having no exudation for 48 weeks while undergoing intravitreal anti-VEGF injections every 12 to 16 weeks. The rate and time of recurrences, best-corrected visual acuity (BCVA), central subfield thickness (CST), number of visits, and reactivity to anti-VEGF were determined after the suspension of the anti-VEGF treatments. RESULTS: In 34 eyes of 34 patients, 17 eyes (50.0%) had a recurrence during the 24-month follow-up period. The median time of a recurrence was 10 months. The BCVA was maintained for 24 months after the suspension regardless of the development of any recurrences. In 41.7% of the eyes that resumed treatment, the duration of exudation suppression by the anti-VEGF therapy was shorter than 12 weeks during the 12 months after restarting the anti-VEGF treatments. There was a significant increase in the number of visits during the first year after beginning the suspension versus during the 1 year before the suspension (non-recurrence group; P = 0.007, recurrence group; P = 0.001). CONCLUSION: Although one-half of the eyes had a recurrence within 24 months after a suspension of anti-VEGF treatment, the BCVA was maintained after a resumption of the anti-VEGF treatments. However, the number of hospital visits increases regardless of the recurrences and the lesion stability is altered by the anti-VEGF suspension. Clinicians should explain both the advantages and disadvantages of anti-VEGF suspension to nAMD patients.

Progress of Diabetic Macular Edema after Loading Injection of Anti-Vascular Endothelial Growth Factor Agents in Real-World Cases.

Background and Objectives: To evaluate the recurrence of diabetic macular edema (DME) after loading an injection of anti-VEGF agents by a pro re nata (PRN) protocol using central retinal thickness (CRT) as a re-injection criterion. Materials and Methods: This is a retrospective, observational single-center study. DME patients with a central retinal thickness (CRT) over 350 µm received a PRN injection of anti-VEGF agents following one to three consecutive monthly loading injections (bevacizumab, ranibizumab, and aflibercept) for 6 months from January 2012 to June 2019. Results: We enrolled a total of 72 eyes for loading injections and the mean CRT improved from 434.04 ± 139.4 µm (before treatment) to 362.9 ± 125.0 µm after the loading injection. One week after injection, 36 eyes (50%) obtained a CRT of ≤350 µm. Fourteen eyes (19.4%) remained with a CRT of ≤350 µm for 6 months without additional injections. A total of 22 eyes (30.6%) had a CRT of >350 µm at 6 months. Fifteen eyes did not receive additional injections because of visual improvement. Conclusions: About 20% of DME patients can be maintained at a CRT of ≤350 µm for 6 months with only a loading injection. However, there is a tendency to delay additional injections for patients with recurrences using PRN protocol.

Case of cystoid macular edema induced by systemic administration of paclitaxel: evaluations with electroretinograms.

PURPOSE: To report abnormal full-field electroretinograms (ERGs) in a patient with cystoid macular edema (CME) induced by systemic paclitaxel. METHODS: This is an observational case report. Full-field ERGs were recorded to evaluate the retinal function using the RETeval system and conventional ERGs using contact lens electrodes with built-in white light-emitting diodes. Optical coherence tomography (OCT) was also used to assess the retinal morphology. RESULTS: A 70-year-old man, who was diagnosed with gastric cancer, had undergone gastrectomy. Subsequently, systemic paclitaxel was administered once a week as an adjuvant therapy. After the tenth course of paclitaxel, he experienced blurred vision in both eyes and visited our department of ophthalmology. OCT revealed the presence of CME in both eyes, and the RETeval flicker ERGs showed a marked reduction in the amplitudes and a prolongation of the implicit times in both eyes. Conventional ERGs showed that the amplitudes of the oscillatory potentials (OPs) were also severely attenuated. The abnormal OCT findings and reduced visual acuity recovered to normal at 1 and 2 months, respectively, after the discontinuation of paclitaxel. However, the flicker ERGs did not recover to normal values until 4 months after the discontinuation of paclitaxel. CONCLUSION: These results suggest that the ERGs can be used to monitor the changes in the overall retinal function in patients receiving paclitaxel.

Case of lens-induced uveitis associated with supernormal flicker ERG amplitudes after cataract surgery.

PURPOSE: To report our findings in a case of lens fragment-induced uveitis associated with supernormal flicker electroretinograms (ERGs) twenty months after the cataract surgery. METHODS: This is an observational case report. Full-field flicker ERGs were recorded with the RETeval system. Optical coherence tomography (OCT) and slit-lamp biomicroscopy were used to assess the uveitis during the follow-up period. RESULTS: A 70-year-old man, who had undergone cataract surgery 20 months earlier, visited our hospital with a complaint of decreased vision in his right eye. Slit-lamp biomicroscopy revealed corneal edema and a lens fragment was detected in the inferior part of the anterior chamber. OCT showed cystoid macular edema, and flicker ERGs showed a marked increase in the amplitude and a delay in the implicit time in the right eye. These abnormalities of the flicker ERGs improved gradually after the removal of lens fragment and application of topical anti-inflammatory medications. CONCLUSION: Our case of lens-induced uveitis had supernormal flicker ERG amplitudes. Clinicians should be aware that eyes with uveitis can have larger-than-normal ERG amplitudes.

Review of clinical studies and recommendation for a therapeutic flow chart for diabetic macular edema.

Diabetic macular edema (DME), characterized by exudative fluid accumulation in the macula, is the most common form of sight-threatening retinopathy in patients with diabetes. The management of DME has changed considerably in recent years, especially following the development of intravitreal anti-vascular endothelial growth factor therapy which has emerged as a first-line therapy for center-involved DME. Laser treatment, intravitreal steroid therapy, and vitrectomy are also important treatment options for DME. We believe that it is important to choose the most appropriate treatment option for DME based on the clinical evidences, in addition to the careful consideration of individual patients' general or ocular condition, DME characteristics, patients' motivation, and compliance to the treatment in real-world clinical practice. In this review, we have summarized important clinical evidences for the main treatments for DME, presented an expert review for these evidences, and proposed a recommended therapeutic flow chart for DME. We hope that our review of the clinical evidences and the recommended therapeutic flow chart for DME will contribute to better treatment outcome for DME.

Cerebral trauma-induced dyschromatopsia in the left hemifield: case presentation.

BACKGROUND: Acquired color anomalies caused by cerebral trauma are classified as either achromatopsias or dyschromatopsias (Zeki, Brain 113:1721-1777, 1990). The three main brain regions stimulated by color are V1, the lingual gyrus, which was designated as human V4 (hV4), and the fusiform gyrus, designated as V4α. (Zeki, Brain 113:1721-1777, 1990). An acquired cerebral color anomaly is often accompanied by visual field loss (hemi- and quadrantanopia), facial agnosia, prosopagnosia, visual agnosia, and anosognosia depending on the underlying pathology (Bartels and Zeki, Eur J Neurosci 12:172-193, 2000), (Meadows, Brain 97:615-632, 1974), (Pearman et al., Ann Neurol 5:253-261, 1979). The purpose of this study was to determine the characteristics of a patient who developed dyschromatopsia following a traumatic injury to her brain. CASE PRESENTATION: The patient was a 24-year-old woman who had a contusion to her right anterior temporal lobe. After the injury, she noticed color distortion and that blue objects appeared green in the left half of the visual field. Although conventional color vision tests did not detect any color vision abnormalities, short wavelength automated perimetry (SWAP) showed a decrease in sensitivity consistent with a left hemi-dyschromatopsia. Magnetic resonance imaging (MRI) detected abnormalities in the right fusiform gyrus, a part of the anterior temporal lobe. At follow-up 14 months later, subjective symptoms had disappeared, but the SWAP abnormalities persisted and a thinning of the sectorial ganglion cell complex (GCC) was detected. CONCLUSION: The results indicate that although the subjective symptoms resolved early, a reduced sensitivity of SWAP remained and the optical coherence tomography (OCT) showed GCC thinning. We conclude that local abnormalities in the anterior section of fusiform gyrus can cause mild cerebral dyschromatopsia without other symptoms. These findings indicate that it is important to listen to the symptoms of the patient and perform appropriate tests including the SWAP and OCT at the early stage to objectively prove the presence of acquired cerebral color anomaly.

Effect of Leaking Foveal Microaneurysms on the Treatment of Center-Involving Diabetic Macular Edema: A Pilot Study.

PURPOSE: Evaluate the effect of foveal leaking microaneurysms (MAs) on the required number of intravitreal ranibiz-umab (IVR) injections in the treatment of center-involving diabetic macular edema (DME) when treated with focal/grid laser. DESIGN: A pilot study of prospective, nonrandomized, multicenter clinical trial. METHODS: This study enrolled 21 eyes with DME for which pro re nata IVR injections were combined with short-pulse focal/grid laser. At 12 months, best-corrected visual acuity (BCVA), central subfield macular thickness (CMT), and the required number of IVRs to maintain CMT < 300 µm were compared between eyes with or without foveal leaking MAs, termed the MA(+) and MA(-) groups, respectively. RESULTS: Significant CMT improvements (p < 0.0001) and increased BCVA of 4.0 ± 8.5 letters were observed at 12 months. The MA(-) group required significantly fewer IVRs than did the MA(+) group (mean: 4.9 ± 3.0 vs. 8.6 ± 3.0; p = 0.0306). In the latter 6 months of the 1-year follow-up, 50% (4/8) of MA(-) eyes did not require any IVR administration to sustain CMT < 300 µm. CONCLUSIONS: A combination therapy of short-pulse focal/grid laser and reduced IVR injections appeared noninferior to previous reports of IVR monotherapy. Further large-scale investigations are warranted.

Short-Term Results of Intravitreal Triamcinolone Acetonide Combined with Cataract Surgery for Diabetic Macular Edema in Japan: In the Era of Anti-Vascular Endothelial Growth Factor Therapy.

PURPOSE: To evaluate the effectiveness of an intravitreal triamcinolone acetonide injection (IVTA) combined with cataract surgery for diabetic macular edema (DME) resistant to anti-vascular endothelial growth factor (anti-VEGF) therapy. PROCEDURE: IVTA combined with cataract surgery was performed on 29 eyes of patients with DME (aged 70.5 ± 6.2 years) who were refractive to anti-VEGF treatments. The visual acuity, central retinal thickness (CRT), and the central retinal sensitivity were assessed at 1, 4, 12, and 24 weeks after the treatment. RESULTS: The visual acuity improved significantly from 0.49 ± 0.30 logMAR units to 0.35 ± 0.33 logMAR units at 24 weeks after the treatment (p < 0.05; repeated ANOVA). The CRT decreased significantly from 435.1 ± 112.3 µm to 350.8 ± 123.3 µm at 12 weeks after the treatment (p < 0.05). The retinal sensitivity threshold also improved significantly from 18.2 ± 4.3 dB to 20.4 ± 3.8 dB at 4 weeks after the treatment (p < 0.05). CONCLUSIONS: IVTA combined with cataract surgery is effective for successful treatment of eyes with DME refractive to anti-VEGF therapy.

Effect of intravitreal ranibizumab on the ocular circulation of the untreated fellow eye.

PURPOSE: To evaluate the effects of unilateral intravitreal ranibizumab (IVR) on the ocular circulation of the fellow eyes. METHODS: Fifteen eyes of 15 patients with macular edema (average age 69.6 ± 11.8 years) were studied. Eleven eyes had diabetic macular edema (DME) and four eyes had macular edema associated with a branch retinal vein occlusion. Each eye received 0.5 mg of IVR. The blood circulation on the optic nerve head of the treated and untreated eyes were determined by laser speckle flowgraphy (LSFG, Softcare Co., Ltd) before, 1 day, and 1 week after the IVR. The mean blur rate (MBR) and the relative changes of the MBRs determined as dMBR(%) = 100-(MBR before/MB after) × 100) were evaluated. The central macular thickness (CMT) and the rate of reduction in the thickness (dCMT = 100-(CMT before/CMT after) × 100) were also evaluated. RESULTS: The mean dMBR was significantly higher in the treated eyes than the untreated eyes at 1 day (-16.4 ± 17.0% vs 2.31 ± 19.3%) and at 1 week (-12.0 ± 14.6% vs 4.50 ± 25.9%) after the IVR (P = 0.02, paired t tests). CONCLUSION: These findings indicate that if ranibizumab enters the systemic circulation, the concentration is not high enough to affect the ocular circulation of the fellow eyes.

[Intravitreal Triamcinolone Acetonide for Persistent Diabetic Macular Edema after Vitrectomy].

PURPOSE: To determine whether intravitreal triamcinolone acetonide (IVTA) is effective in resolving edema in eyes with persistent diabetic macular edema (DME) after vitrectomy. PATIENTS AND METHODS: Sixteen eyes of 16 patients were given 4 mg IVTA after vitrectomy for DME. The best-corrected visual acuity (BCVA), central macular thickness (CMT), and average threshold (AT) of the central retina were determined during the 24 weeks follow-up period. Patients were divided into two groups; early treatment group and late treatment group. RESULTS: The BCVA was significantly improved at 12 weeks, the CMT was significantly improved at 24 weeks, and the AT was significantly improved at 4 weeks after IVTA (repeated ANOVA, p < 0.05). The BCVA was more significantly improved in the early treatment group than in the late treatment group at 4 and 12 weeks (unpaired t test, p < 0.05). CONCLUSION: Our results indicate that IVTA should be considered as treatment for patients with persistent DME after vitrectomy, especially with early treatment patients.

Inhibition of EGF signaling protects the diabetic retina from insulin-induced vascular leakage.

Diabetes mellitus is a disease with considerable morbidity and mortality worldwide. Breakdown of the blood-retinal barrier and leakage from the retinal vasculature leads to diabetic macular edema, an important cause of vision loss in patients with diabetes. Although epidemiologic studies and randomized clinical trials suggest that glycemic control plays a major role in the development of vascular complications of diabetes, insulin therapies for control of glucose metabolism cannot prevent long-term retinal complications. The phenomenon of temporary paradoxical worsening of diabetic macular edema after insulin treatment has been observed in a number of studies. In prospective studies on non-insulin-dependent (type 2) diabetes mellitus patients, a change in treatment from oral drugs to insulin was often associated with a significant increased risk of retinopathy progression and visual impairment. Although insulin therapies are critical for regulation of the metabolic disease, their role in the retina is controversial. In this study with diabetic mice, insulin treatment resulted in increased vascular leakage apparently mediated by betacellulin and signaling via the epidermal growth factor (EGF) receptor. In addition, treatment with EGF receptor inhibitors reduced retinal vascular leakage in diabetic mice on insulin. These findings provide unique insight into the role of insulin signaling in mediating retinal effects in diabetes and open new avenues for therapeutics to treat the retinal complications of diabetes mellitus.

Multiple evanescent white dot syndrome in highly myopic eye in which fundus autofluorescence was diagnostically useful: A case report.

RATIONALE: Multiple evanescent white dot syndrome (MEWDS) is characterized by multiple white dots in the posterior pole of the eye, but its diagnosis can be difficult in cases when the white dots are not visible. We report an atypical case of MEWDS that developed in pathologic myopia. PATIENT CONCERN: A 42-year-old woman presented with floater and reduced and distorted vision in the right eye that she noted 3 days earlier. DIAGNOSIS: The right eye was highly myopic at -17.0 diopters, and her decimal best-corrected visual acuity was reduced to 0.2 (20/100). Fundus examinations revealed no abnormalities other than myopic fundus changes and previous laser photocoagulation spots. However, fundus autofluorescence (FAF) showed multiple hyperfluorescent dots, and optical coherence tomography showed a high reflective lesion on the retinal pigmental epithelium at the fovea. Adjustments of the brightness and contrast of the conventional fundus images revealed white dots in the same location as the hyperfluorescent spots seen in the FAF images. We diagnosed her with MEWDS. INTERVENTIONS: We treated her with systemic administration of 20 mg prednisolone and the dose of prednisolone was reduced by 5 mg every 4 weeks. OUTCOMES: The optical coherence tomography and FAF findings gradually normalized, and 5 months later, her decimal visual acuity was restored to 1.0 (20/20). LESSONS: It was suggested that white dots typical to MEWDS may not be evident in pathologic myopia, and FAF images and the brightness and contrast adjustment of fundus images were useful in the diagnosis of atypical MEWDS.

Suspension of Anti-VEGF Treatment Does Not Affect Expansion of RPE Atrophy in Neovascular Age-Related Macular Degeneration.

PURPOSE: To determine whether atrophy of the retinal pigment epithelium (RPE) in eyes with neovascular age-related macular degeneration (nAMD), which meets the criteria for the suspension of anti-vascular endothelial growth factor (anti-VEGF) treatment, is associated with anti-VEGF treatments. METHODS: Twelve eyes of 12 patients with nAMD who began anti-VEGF treatment and were followed for 1 year after meeting the criteria for the suspension of anti-VEGF were studied. Six eyes of six patients were placed in the continuation group, and six eyes of six patients were placed in the suspension group. The RPE atrophic area at the time of the last anti-VEGF treatment was set as the baseline size and that at 12 months after the baseline (Month 12) was taken as the final size. A comparison of the expansion rate of RPE atrophy between the two groups was made by the square-root transformed differences. RESULTS: The expansion rate of atrophy was 0.55 (0.43, 0.72) mm/year in the continuation group and 0.33 (0.15, 0.41) mm/year in the suspension group. This difference was not significant. (p = 0.29). CONCLUSIONS: Suspension of anti-VEGF treatments in eyes with nAMD does not alter the expansion rate of RPE atrophy.

Transient Increase of Flicker Electroretinography Amplitudes after Cataract Surgery: Association with Postoperative Inflammation.

Purpose: To determine the characteristics and cause of the increase in the amplitude of flicker electroretinography (ERG) after cataract surgery. Design: Prospective, observational clinical study. Participants: Thirty patients who underwent cataract surgery. Methods: Flicker ERGs were recorded with the RETeval system without mydriasis. The central macular thickness (CMT) was measured by OCT and the aqueous flare value (AFV) by laser flare-cell photometry. These examinations were performed before surgery and 1 day, 1 week, 1 month, 2 months, and 3 months after surgery. Linear regression analysis through the origin was used to compare the correlations between the relative changes in flicker ERG amplitudes and the changes in the CMT and AFV at different times after the surgery. Main Outcome Measures: The amplitude of flicker ERGs, CMT, and AFV. Results: The mean amplitude of flicker ERGs increased significantly by 31% at 1 week after surgery (P < 0.001); a significant increase in the amplitudes was not present at 3 months after the surgery. The mean AFV was significantly increased at 1 day after surgery (P < 0.001), and the CMT was significantly increased at 1 to 3 months after surgery (P < 0.001). The changes in flicker ERG amplitudes at 1 week after surgery were significantly associated with the changes in the CMT at 1 to 3 months after surgery (P < 0.05), and they were weakly associated with the changes in AFV at 1 day after surgery (P = 0.05). Conclusions: These results suggest that the increase in the amplitude of flicker ERGs after cataract surgery is a transient phenomenon that has a peak at 1 week after surgery. The increase of flicker ERG amplitude was associated with measures that are frequently used to evaluate postoperative inflammation. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

Comparisons of Clinical Characteristics and Surgical Outcomes of Epiretinal Membrane Foveoschisis to Typical Epiretinal Membrane.

Epiretinal membrane (ERM) foveoschisis is a recently proposed clinical entity. The purpose of this study was to compare the clinical characteristics and surgical outcomes of eyes with ERM foveoschisis to those of typical ERM. The medical records of all patients with ERM-related disorders examined between 2011 and 2020 were reviewed. ERM foveoschisis was defined by the clinical criteria proposed by an international panel of experts on ERMs. The background factors, clinical characteristics, and surgical outcomes of ERM foveoschisis were compared to those of typical ERM. Forty eyes with ERM foveoschisis were compared to 333 eyes with typical ERM. The percentage of women was significantly higher in the ERM foveoschisis group (92.5%) than in the typical ERM group (48.9%, p < 0.001). The central macular thickness (CMT) was significantly thinner in the ERM foveoschisis group (340 ± 110 µm) than in the typical ERM groups (476 ± 111 µm, p < 0.01). The degree of improvement in the best-corrected visual acuity (BCVA) three months after the surgery did not differ between the two groups (p = 0.59). These results suggest that the ERM foveoschisis is more likely to occur in women and that the prognosis after surgery is comparable to typical ERM.

CEP-1347 Dually Targets MDM4 and PKC to Activate p53 and Inhibit the Growth of Uveal Melanoma Cells.

Uveal melanoma (UM) is among the most common primary intraocular neoplasms in adults, with limited therapeutic options for advanced/metastatic disease. Since UM is characterized by infrequent p53 mutation coupled with the overexpression of MDM4, a major negative regulator of p53, we aimed to investigate in this study the effects on UM cells of CEP-1347, a novel MDM4 inhibitor with a known safety profile in humans. We also examined the impact of CEP-1347 on the protein kinase C (PKC) pathway, known to play a pivotal role in UM cell growth. High-grade UM cell lines were used to analyze the effects of genetic and pharmacological inhibition of MDM4 and PKC, respectively, as well as those of CEP-1347 treatment, on p53 expression and cell viability. The results showed that, at its clinically relevant concentrations, CEP-1347 reduced not only MDM4 expression but also PKC activity, activated the p53 pathway, and effectively inhibited the growth of UM cells. Importantly, whereas inhibition of either MDM4 expression or PKC activity alone failed to efficiently activate p53 and inhibit cell growth, inhibition of both resulted in effective activation of p53 and inhibition of cell growth. These data suggest that there exists a hitherto unrecognized interaction between MDM4 and PKC to inactivate the p53-dependent growth control in UM cells. CEP-1347, which dually targets MDM4 and PKC, could therefore be a promising therapeutic candidate in the treatment of UM.