Purpose:Prevalence of diabetic retinopathy closely depends on the duration of diabetes and severity of hyperglycemia. Experimental models have shown that high glucose initiates many metabolic, molecular and epigenetic changes in the retina before vascular histopathology is detectable. Several LncRNAs (RNAs with >200bp and no reading frame) are also aberrantly expressed in the retina in diabetes. These RNAs have high organ and cell specificity and show minimal gradual instability in plasma. Our goal was to examine the utility of aberrantly expressed retinal LncRNAs (nuclear DNA-encoded NEAT1, HOTAIR, HOTTIP, MALAT1, H19 and Meg3 and mitochondrial DNA-encoded CytB) in diabetes as possible biomarkers of diabetic retinopathy. Methods:Plasma LncRNAs were analyzed by qRT-PCR in diabetic patients with proliferative (PDR), or no retinopathy (No-DR), and in rats with streptozotocin-induced diabetes for two to six months. The results were confirmed in the retina from donors with diabetic retinopathy and from diabetic rats. Results:Plasma NEAT1, HOTAIR, MALAT1 and HOTTIP were upregulated and Meg3 and CytB were downregulated in No-DR and PDR groups and retina from human donors with diabetic retinopathy. Although these LncRNAs were also aberrantly expressed in plasma and retina within four to six months of diabetes in rats, NEAT1 and CytB had abnormal expression within two months of diabetes (without any retinal vascular histopathology). Conclusions:NEAT1 and CytB have consistent expression patterns in plasma from diabetic patients and plasma and retina from rodents. Translational Relevance:Plasma NEAT1 and CytB could serve as possible early noninvasive biomarkers of retinopathy in diabetic patients.

A 67-year-old woman with history of mild suture hyper-sensitivity presented with localized scleritis after strabismus surgery. After infection was ruled out, the patient was prescribed topical and systemic non-steroidal anti-inflammatory drugs and systemic steroids, which led to full clinical resolution. [ J Pediatr Ophthalmol Strabismus . 2024;61(1):e4–e6.]

Abstract Background To evaluate the accuracy of intravitreal injection volume of the pre-filled syringe (PFS) in which aflibercept is packaged compared to the BD Luer-Lok 1-mL syringe. Methods Ophthalmologists injected their typical intravitreal volume for aflibercept using either the PFS or BD Luer-Lok 1-mL syringe for 5 times each. The injected fluid was weighed using a micro-scale and converted to volume. The volume of fluid injected was also evaluated when the 0.05 mL line on the PFS was lined up to the tip or base of the dome-shaped plunger. Results Injection volume was measured for 12 physicians. The average injected fluid volume was 74.22 ± 15.87 µL for PFS and 53.42 ± 4.61 µL for the BD Luer-Lok 1-mL syringe (p < 0.0001). The average deviation in volume injected for the PFS was higher compared to the BD Luer-Lok 1-mL syringe (11.36 µL vs. 3.35 µL, p < 0.0001). When the PFS was lined up with the tip of the dome-shaped plunger at the 0.05-mL line, the average injected volume was 71.03% higher. Conclusions The intravitreal injection volume and variability using the new PFS were significantly higher than the volume injected using the BD Luer-Lok 1-mL syringe previously used, potentially leading to higher rates of visually significant elevation of intraocular pressures.

Purpose: To describe the diagnostic and treatment challenges of a case of presumed acquired macula-involving toxoplasmosis retinochoroiditis. Methods: Case report of a woman with congenital long QT syndrome presenting with retinochoroiditis after undergoing a cardiac procedure. Laboratory analysis, ocular fluid biopsy, and multimodal imaging were obtained. Results: Ophthalmic examination was significant for decreased vision and a macula-involving chorioretinal lesion concerning for endogenous endophthalmitis. Multimodal imaging showed a focal, full-thickness necrotizing process associated with vitritis, retinal edema, and choroidal thickening. Analysis of peripheral blood revealed elevated serum toxoplasma Immunoglobulin G titers. Blood cultures and a transesophageal echocardiogram were negative for endocarditis. Aqueous and vitreous specimens were negative for an infectious polymerase chain reaction panel, including toxoplasmosis and negative bacterial and fungal cultures. A diagnosis of presumed acquired toxoplasmosis retinochoroiditis was made and treated with a combination of oral and intravitreal antiparasitic medications resulting in healing of the retinochoroiditis. Conclusion: To the authors' knowledge, this is the first reported case of acquired toxoplasmosis retinochoroiditis in an immunocompetent patient with congenital long QT syndrome masquerading as endogenous endophthalmitis. The association of congenital long QT syndrome and a recent cardiac procedure with a risk for endogenous endophthalmitis complicated the diagnosis, clinical course, and treatment options. Our case emphasizes the importance of a thorough patient history, comprehensive clinical examination, and supportive multimodal imaging that were used to characterize the infectious process and guide empirical treatment. In addition, laboratory analysis, comanagement with other specialists, and evaluating the response to antitoxoplasma therapy were all instrumental in the eventual diagnosis and treatment of ocular toxoplasmosis in this atypical case.

OBJECTIVE:To describe opioid prescribing practices of ophthalmology subspecialties and determine whether opioid prescribing has decreased during the public health crisis. DESIGN:Retrospective cohort study. PARTICIPANTS:Ophthalmologists prescribing at least 11 medications billed to the Medicare Part D prescription drug plan. METHODS:Publicly available Medicare data sets based on claims from the years 2016, 2017, and 2018 were used. Fellowship status was assumed based on subspecialty society membership or use of specified Current Procedural Terminology codes. The main outcome was the percentage of physicians in each subspecialty prescribing opioids. RESULTS:The database included 19,762, 19,790, and 19,840 ophthalmologists in the years 2016, 2017, and 2018, respectively. Only the subspecialties of comprehensive ophthalmology (43.5% vs 39.6% vs 35.7%; p < 0.001; φc = 0.066), retina (66.5% vs 60.7% vs 54.5%; p < 0.001; φc = 0.101), cornea (82.8% vs 83.9% vs 77.2%; p = 0.03; φc = 0.076), and glaucoma (53.4% vs 46.4% vs 42.0%; p < 0.001; φc = 0.094) underwent a small but significant reduction in the proportion of physicians prescribing opioids. The subspecialties of oculoplastics (86%-88.8%), cornea (77.2%-82.8%), retina (54.5%-66.5%), and pediatrics (51.5%-57.9%) had the highest percentage of physicians prescribing opioids. The subspecialties of glaucoma, uveitis, and comprehensive ophthalmology had the lowest percentage of opioid prescribers. Among physicians with more than 10 opioid claims, median opioid claims did not change drastically. Opioids contributed only a small proportion of medication claims for all subspecialties. CONCLUSION:All subspecialties experienced either a small reduction or no significant change in the percentage of opioid prescribers during the period analyzed. We hope to encourage collaboration between ophthalmology subspecialties in striving to reduce opioid prescribing. Further studies are needed to better fine-tune opioid prescribing practices.

Purpose: This study determines whether fluorescein angiography (FA) with a 250-mg dose of fluorescein (half dose) is equal in quality to the standard 500-mg dose of fluorescein (full dose) when using digital ultra-widefield (UWF) technology. Methods: In a randomized, prospective study using a UWF imaging system, FAs performed with half dose were compared with angiograms performed with full dose. Imaging studies were reviewed by 4 reviewers based on 6 characteristics: dye transit, macrovasculature, macula detail, microvasculature, leakage, and overall quality. The scores for macrovasculature, macula detail, microvasculature, and overall quality were converted to a fuzzy rating score to confirm results. Results: Seventy-nine FAs from 67 patients were reviewed for this study, including 12 patients who had both half-dose and full-dose FAs. Of all the factors studied, only microvasculature received a significantly different score between full dose and half dose that was confirmed by the fuzzy rating scale (3.79 vs 3.53; P=.04). Among those eyes that received both full and half dose, there was no significant difference in any of the 6 factors. Conclusions: In a UWF imaging system, aside from looking at fine microvascular abnormalities, the 250-mg dose of fluorescein provided similar results to a 500-mg dose. The images were not significantly different in overall quality.

Background: Adeno-associated Virus (AAV) vectors are the most promising vehicles for therapeutic gene delivery to the retina. To develop a practical gene delivery tool, achieving high AAV transduction efficiency in specific cell types is often required. AAV-mediated targeted expression in retinal bipolar cells is needed in certain applications such as optogenetic therapy, however, the transduction efficiency driven by endogenous cell-specific promoters is usually low. Methods that can improve AAV transduction efficiency in bipolar cells need to be developed. Objective: The study aimed to examine the effect of proteasome inhibitors on AAV-mediated transduction efficiency in retinal bipolar cells. Methods: Quantitative analysis of fluorescent reporter protein expression was performed to assess the effect of two proteasome inhibitors, doxorubicin and MG132, on AAV-mediated transduction efficiency in retinal bipolar cells in mice. Results: Our results showed that doxorubicin can increase the AAV transduction efficiency in retinal bipolar cells in a dose-dependent manner. We also observed doxorubicin-mediated cytotoxicity in retinal neurons, but the cytotoxicity could be mitigated by the coapplication of dexrazoxane. Three months after the coapplication of doxorubicin (300 μM) and dexrazoxane, the AAV transduction efficiency in retinal bipolar cells increased by 33.8% and no cytotoxicity was observed in all the layers of the retina. Conclusion: Doxorubicin could enhance the AAV transduction efficiency in retinal bipolar cells in vivo. The potential long-term cytotoxicity caused by doxorubicin to retinal neurons could be partially mitigated by dexrazoxane. The coapplication of doxorubicin and dexrazoxane may serve as a potential adjuvant regimen for improving AAV transduction efficiency in retinal bipolar cells.

Hintergrund: Monoklonale Gammopathie unklarer Signifikanz (MGUS) ist eine Plasmazelldyskrasie und Vorstufe des Multiplen Myeloms. Okuläre Manifestationen sind bekannt, bislang wurde jedoch noch kein Zusammenhang mit einer Autoimmun-Retinopathie nachgewiesen. Fallvorstellung: Eine 57-jährige Frau stellte sich mit seit einem Jahr bestehendem progressiven, beidseitigen, peripheren Verlust des Sehvermögens, Photopsien und Nachtblindheit vor. Die Augenhintergrunduntersuchung und umfassende ergänzende Tests legten den Verdacht einer hereditären oder einer Autoimmun-Retinopathie nahe. Man stellte bei der Patientin antiretinale Antikörper gegen Carboanhydrase II- und Enolase-Proteine bei einem negativen Gen-Panel für Netzhautdystrophie fest. Die Untersuchung auf Malignität war negativ, aber bei der Patientin wurde MGUS, eine prämaligne Erkrankung, diagnostiziert. Die Patientin wurde mit Immunsuppressiva behandelt, wobei sie im Hinblick auf ihre Symptomatik und die augenmedizinischen Untersuchungen am deutlichsten auf Rituximab ansprach. Schlussfolgerung: MGUS sollte bei Patienten ohne andere autoimmune oder maligne Krankheitsprozesse als potenziell ätiologisch für eine Autoimmun-Retinopathie in Betracht gezogen werden. Eine Behandlung mit Immunsuppressiva kann bei der Begrenzung der Krankheitsprogression von Nutzen sein, und Rituximab erweist sich bei Patienten mit Retinopathie, die auf andere Wirkstoffe nicht ansprechen, als wirksam.

The loss of photoreceptors in individuals with retinal degenerative diseases leads to partial or complete blindness. Optogenetic therapy is a promising approach for restoring vision to the blind. Multiple strategies have been employed by targeting genetically encoded light sensors, particularly channelrhodopsins, to surviving retinal neurons in animal models. In particular, the strategy of targeting retinal bipolar cells has commonly been expected to result in better vision than ubiquitous expression in retinal ganglion cells. However, a direct comparison of the channelrhodopsin-restored vision between these two strategies has not been performed. Here, we compared the restored visual functions achieved by adenoassociated virus (AAV)-mediated expression of a channelrhodopsin in ON-type bipolar cells and retinal ganglion cells driven by an improved mGluR6 promoter and a CAG promoter, respectively, in a blind mouse model by performing electrophysiological recordings and behavioral assessments. Unexpectedly, the efficacy of the restored vision based on light sensitivity and visual acuity was much higher following ubiquitous retinal ganglion cell expression than that of the strategy targeting ON-type bipolar cells. Our study suggests that, at least based on currently available gene delivery techniques, the expression of genetically encoded light sensors in retinal ganglion cells is likely a practical and advantageous strategy for optogenetic vision restoration.

Purpose: To report a novel case of dark without pressure in a patient with a choroidal osteoma. To our knowledge, this association has not been previously reported. Methods: Observational case report. Review of clinical examination and multi-modal imaging findings in a patient with a choroidal osteoma and dark without pressure. Results: A 21-year-old African American woman with no significant past medical history presented with a large, unilateral, juxtapapillary, subretinal, orange-colored, ovoid-shaped lesion with macular involvement. An overlying area of mottled pigmentary changes, fibrosis, and atrophy were present. Adjacent to and surrounding the osteoma was an annular band of hyperpigmented mid-peripheral retina with a sharply demarcated scalloped border that abruptly changed to normal-appearing peripheral retina. Multi-modal imaging including wide-field fluorescein angiography, optical coherence tomography, and ophthalmic B-scan were performed. The funduscopic and imaging findings were consistent with a diagnosis of choroidal osteoma and dark without pressure. Conclusion: The examination and imaging findings in this patient suggest a unique association between two relatively uncommon lesions, choroidal osteoma, and dark without pressure. Although these two lesions may simply be coinciding in the same eye, there may be an association with space-occupying lesions causing a change in photoreceptor structure.

In this chapter, we will give a brief overview of fundus photography, SLO, and OCT while discussing photoacoustic imaging potential as the next major ocular imaging modality.

Purpose: To report a case of inducible transient central retinal artery vasospasm with associated imaging. Methods: Observational case report. Results: A 51-year-old man presented for outpatient follow-up for recurrent inducible transient vision loss in his right eye. He experienced an episode during examination and was found to have central retinal artery vasospasm. Fundus photography and fluorescein angiography obtained during his vasospastic attack confirmed retinal arterial vasospasm. Treatment with a calcium-channel blocker (nifedipine) has been effective in preventing recurrent attacks. Conclusion: Idiopathic primary vasospasm is a rare cause of transient vision loss that is difficult to confirm because of the transient nature. We obtained imaging showing the initiation and resolution of the vasospastic event. The patient was then successfully treated with a calcium-channel blocker.

Background Monoclonal gammopathy of undetermined significance (MGUS) is a plasma cell dyscrasia and precursor to multiple myeloma. It has known ocular manifestations, but has not previously been shown to have an association with autoimmune retinopathy. Case presentation A 57 year-old female presented with 1 year of progressive, bilateral, peripheral vision loss, photopsias, and nyctalopia. Her fundus examination and extensive ancillary testing were concerning for hereditary versus autoimmune retinopathy. The patient was found to have anti-retinal antibodies against carbonic anhydrase II and enolase proteins with a negative genetic retinal dystrophy panel. Malignancy work-up was negative, but the patient was diagnosed with MGUS, a premalignant condition. The patient was treated with immunosuppressive therapies, with rituximab demonstrating the most robust therapeutic response with respect to patient symptoms and ophthalmic testing. Conclusions MGUS should be considered as a potential etiology of autoimmune retinopathy in patients without other autoimmune or malignant disease processes. Immunosuppressive therapy may be helpful in limiting disease progression, with rituximab showing efficacy in retinopathy refractory to other agents.

PURPOSE:To report a case of optic pit maculopathy with retinoschisis-like edema with a rare finding of retinal telangiectasia.METHODS:Retrospective case report.RESULTS:A 22-year-old white man with a right optic pit presented with blurry vision and was found to have optic pit maculopathy with retinoschisis-like macular edema and retinal telangiectasia along the superior-temporal arcade. The patient underwent pars plana vitrectomy with separation of posterior vitreous and inner retinal fenestration. Upon follow-up, retinal telangiectasia was resolved and retinoschisis-like edema was mostly resolved 2 years after surgery.CONCLUSION:Retinal telangiectasia seen in optic disk maculopathy may be secondary to ischemia induced by the intense stretching of the superficial vascular plexus in the inner retina because of macular edema. In our patient, when traction was relieved following surgical intervention, there was remodeling of the superficial vascular plexus that allowed for resolution of the retinal telangiectasia.