Investigating the Utility of Near-Infrared Reflectance Imaging for Diabetic Retinopathy Screening.

BACKGROUND AND OBJECTIVE: We investigated the reliability of near-infrared reflectance (NIR) imaging as a method of assessing severity of diabetic retinopathy (DR). PATIENTS AND METHODS: One hundred ninety-five NIR images were reviewed by two graders for the number of hyporeflective foci, presence or absence of vascular abnormalities, and presumptive DR stage; these were correlated to fundus photography-defined DR stage. Interrater reliability was confirmed via one-way random effects model of intraclass correlation coefficients. Analysis of variance was used in subgroup analysis, receiver operating characteristic (ROC) curves were created to validate reliability of the model, and logistic regression was used to model foci and vascular abnormalities as predictors for moderate or worse disease. RESULTS: A statistically significant difference in mean number of hyporeflective foci was found between no DR and moderate non-proliferative DR (NPDR; P < 0.0001), no DR and severe NPDR (P < 0.001), no DR and proliferative DR (PDR; P < 0.0001), mild and moderate NPDR (P = 0.008), mild and severe NPDR (P < 0.001), and mild NPDR and PDR (P < 0.001). The area under the ROC curve was 0.849 (CI: 0.792 to 0.905). The threshold for detection of moderate NPDR or worse was 4.75 foci, with a sensitivity of 79.0% and a false positive rate of 20.0%. Multivariate logistic regression model incorporating hyporeflective foci with vascular abnormalities (odds ratio [OR] = 1.592, 95% CI: 1.381 to 1.835; P < 0.001) was able to accurately predict moderate disease or worse, just moderate disease (OR = 1.045, 95% CI: 1.003 to 1.089; P = 0.035), severe disease (OR = 1.050, 95% CI: 1.006 to 1.096; P = 0.027), and proliferative disease (OR = 1.050, 95% CI: 1.008 to 1.095; P = 0.018). CONCLUSIONS: NIR imaging may be an adjunct tool in screening for DR. [Ophthalmic Surg Lasers Imaging Retina 2024;55:318-325.].

Conversion to faricimab after prior anti-vascular endothelial growth factor therapy for persistent diabetic macular oedema.

BACKGROUND: To assess the anatomical and functional outcomes in eyes with persistent diabetic macular oedema (pDME) on chronic anti-vascular endothelial growth factor therapy switched to intravitreal faricimab. METHODS: Patients with pDME on chronic anti-vascular endothelial growth factor therapy that were switched to faricimab and received at least three injections at our institution between April 2022 and May 2023 were included in this study. Patients were excluded if they had complete response to previous treatment but were switched to extend treatment intervals if they had steroid or laser treatment for DME within 6 months prior to switch. Clinical and imaging data were extracted from the electronic medical record. Central foveal thickness (CFT) and Snellen visual acuity (VA) were obtained before and after three intravitreal faricimab injections. Generalised estimating equations were used to analyse the change in CFT and VA. RESULT: During the study period, 69 eyes of 53 patients met inclusion criteria. The mean age was 68.6±9.0 years. The mean number of injections prior to switch was 18.1±16.0. Pre-switch mean logarithm of the minimal angle of resolution VA was 0.40±0.30 (Snellen equivalent 20/50) and 0.38±0.27 (Snellen equivalent 20/48) after three faricimab injections (p=0.397). Mean CFT improved from 380±155 microns to 323±147 microns (p<0.001). No ophthalmic or systemic adverse events occurred during the study period. CONCLUSIONS: Intravitreal faricimab can improve anatomic outcomes while maintaining visual acuity in eyes with pDME previously treated with anti-VEGF therapy.

Clinical Outcomes of Faricimab in Patients with Previously Treated Neovascular Age-Related Macular Degeneration.

PURPOSE: To assess the anatomic and functional outcomes in eyes with neovascular age-related macular degeneration (nAMD) previously treated with anti-VEGF therapy in response to intravitreal faricimab. DESIGN: Retrospective, interventional, consecutive case series. SUBJECTS: Patients with previously treated nAMD who received ≥ 4 consecutive injections of faricimab were included. The study period was from March through November 2022. METHODS: Clinical and imaging data were extracted from the electronic medical record. Central foveal thickness (CFT), maximum fibrovascular pigment epithelial detachment (fvPED) height, and Snellen visual acuity (VA) were obtained. Generalized estimating equations were used to analyze the change in CFT, maximum fvPED height, and logarithm of the minimum angle of resolution VA. MAIN OUTCOME MEASURES: Change in CFT, maximum fvPED height, and Snellen VA before faricimab and after ≥ 4 faricimab intravitreal injections. RESULTS: During the study period, 218 eyes of 191 patients met inclusion criteria. Mean age was 79.9 (range, 70.6-89.2) years. The mean number of intravitreal anti-VEGF injections received before faricimab was 34.2 (range, 6.4-62). The following results were found after ≥ 4 faricimab injections. Mean logarithm of the minimum angle of resolution VA before switching to faricimab was 0.58 (Snellen VA ∼20/76; range, 20/22-20/264) and was 0.55 (Snellen VA ∼20/71; range, 20/21-20/235; P = 0.20) after switching. Mean maximum fvPED height was 195.0 (range, 50.2-339.8) µm before switching to faricimab and improved to 165.0 (range, 33.6-296.4; P < 0.001) µm after switching. Mean CFT was 354.8 (range, 184.7-524.9) µm before switching to faricimab and improved to 306.6 (range, 144.4-468.8; P < 0.001) after switching. The proportion of eyes with intraretinal fluid was 36.7% (80/218 eyes) before switching, and decreased to 24.8% (54/218 eyes, P < 0.001) after switching. The proportion of eyes with subretinal fluid was 53.2% (116/218 eyes) before switching and decreased to 26.6% (58/218 eyes, P < 0.001) after switching. CONCLUSIONS: Intravitreal faricimab may improve anatomic outcomes in patients with previously treated nAMD, while maintaining VA in the short-term. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Appropriateness and Readability of ChatGPT-4-Generated Responses for Surgical Treatment of Retinal Diseases.

OBJECTIVE: To evaluate the appropriateness and readability of the medical knowledge provided by ChatGPT-4, an artificial intelligence-powered conversational search engine, regarding common vitreoretinal surgeries for retinal detachments (RDs), macular holes (MHs), and epiretinal membranes (ERMs). DESIGN: Retrospective cross-sectional study. SUBJECTS: This study did not involve any human participants. METHODS: We created lists of common questions about the definition, prevalence, visual impact, diagnostic methods, surgical and nonsurgical treatment options, postoperative information, surgery-related complications, and visual prognosis of RD, MH, and ERM, and asked each question 3 times on the online ChatGPT-4 platform. The data for this cross-sectional study were recorded on April 25, 2023. Two independent retina specialists graded the appropriateness of the responses. Readability was assessed using Readable, an online readability tool. MAIN OUTCOME MEASURES: The "appropriateness" and "readability" of the answers generated by ChatGPT-4 bot. RESULTS: Responses were consistently appropriate in 84.6% (33/39), 92% (23/25), and 91.7% (22/24) of the questions related to RD, MH, and ERM, respectively. Answers were inappropriate at least once in 5.1% (2/39), 8% (2/25), and 8.3% (2/24) of the respective questions. The average Flesch Kincaid Grade Level and Flesch Reading Ease Score were 14.1 ± 2.6 and 32.3 ± 10.8 for RD, 14 ± 1.3 and 34.4 ± 7.7 for MH, and 14.8 ± 1.3 and 28.1 ± 7.5 for ERM. These scores indicate that the answers are difficult or very difficult to read for the average lay person and college graduation would be required to understand the material. CONCLUSIONS: Most of the answers provided by ChatGPT-4 were consistently appropriate. However, ChatGPT and other natural language models in their current form are not a source of factual information. Improving the credibility and readability of responses, especially in specialized fields, such as medicine, is a critical focus of research. Patients, physicians, and laypersons should be advised of the limitations of these tools for eye- and health-related counseling. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Follow-up Rates After Teleretinal Screening for Diabetic Retinopathy: Assessing Patient Barriers to Care.

Purpose: To study patient follow-up after they engage in a teleretinal screening program and to understand potential barriers to care. Methods: This was a retrospective analysis and a prospective study of telephone-based patient interviews of outpatients screened for diabetic retinopathy (DR) through a teleretinal referral system. Results: Of 2761 patients screened through a teleretinal referral program, 123 (4.5%) had moderate nonproliferative DR (NPDR), 83 (3.0%) had severe NPDR, and 31 (1.1%) had proliferative DR. Of the 114 patients with severe NPDR or worse, 67 (58.8%) saw an ophthalmologist within 3 months of referral. Eighty percent of interviewed patients reported they were not aware of the need for follow-up eye appointments. Conclusions: Of patients with severe retinopathy or worse, 58.8% presented for in-person evaluation and treatment within 3 months of screening. Although this result was negatively affected by factors related to the COVID-19 pandemic, key elements of patient education and improved referral strategies to facilitate in-person treatment are essential to improving follow-up after patients engage in telescreening.

Recent advances in the management of proliferative diabetic retinopathy.

PURPOSE OF REVIEW: The prevalence of diabetic retinopathy continues to rise. This review highlights advances in imaging, medical, and surgical management of proliferative diabetic retinopathy (PDR) in recent years. RECENT FINDINGS: Ultra-widefield fluorescein angiography has been shown to better characterize which patients have predominantly peripheral lesions and who may advance to more advanced forms of diabetic retinopathy. This was well demonstrated in DRCR Retina Network's Protocol AA. Protocol S demonstrated that antivascular endothelial growth factor (VEGF) treatment alone can be useful in the management of select PDR patients - particularly those without high-risk features. However, a growing body of literature highlights how lapse in care is a significant concern in PDR patients, and tailoring one's approach to treatment based on patient needs is recommended. In patients with high-risk features or where there is concern for lost-to-follow-up, incorporation of panretinal photocoagulation in the treatment paradigm is recommended. Protocol AB highlighted how patients with more advanced disease may benefit from earlier surgical intervention for earlier visual recovery but that continued anti-VEGF treatment may result in similar visual outcomes over a longer period. Finally, earlier surgical intervention for PDR without vitreous hemorrhage (VH) or retinal detachment is being considered a potential option to minimize treatment burden. SUMMARY: Recent advances in imaging, as well as medical and surgical treatment options for PDR, have provided a deeper understanding of PDR management, which can be optimized for the individual patient.

Two cases of unilateral cone-rod dysfunction presenting in adult females.

PURPOSE: To describe cases of unilateral cone-rod dysfunction presenting in two middle-aged females. METHODS: This case series highlights two middle-aged female patients with progressive visual decline in one eye. Fundus photography, fundus autofluorescence (FAF), spectral-domain optical coherence tomography (SD-OCT), multi-focal electroretinogram (mfERG), full-field electroretinogram(ffERG), and genetic testing were obtained. RESULTS: In the first patient, mfERG showed an extinguished response and ffERG demonstrated markedly reduced a-wave and b-wave amplitudes (more pronounced under photopic conditions) in the right eye. SD-OCT showed attenuation of the ellipsoid zone of the right eye. Similar findings were appreciated in the second patient. Genetic testing in the first patient identified three heterozygous variants in PRPH2, RCBTB1, and USH2A. The second patient was found to have heterozygous variants in BBS1 and ABCA4. CONCLUSION: These two cases add to the literature of case reports of unilateral cone-rod and rod-cone dystrophies. However, the underlying etiology of the unilateral pattern of cone-rod dysfunction and the significance of the heterozygous mutations found in both cases remains uncertain.

Documentation of recovery from vitamin A deficiency-related retinopathy via multimodal imaging and electroretinogram testing.

PURPOSE: To describe vitamin A deficiency using multimodal functional visual assessments and imaging. METHODS/CASE: A 50-year-old female with past medical history significant for Roux-en-Y gastric bypass surgery complained of nyctalopia and "yellowing" of vision. RESULTS: Vitamin A levels were noted to be < 0.06 mg/L (normal 0.3-0.12 mg/L). Fundus examination was notable for peripheral yellow punctate lesions, superior arcuate defects on HVF 30-2 testing, an indistinct ellipsoid zone on SD-OCT, and absent rod responses and severely reduced amplitudes for the cone photoreceptors on full-field ERG. These findings resolved with initiation of parenteral vitamin A supplementation. CONCLUSION: This report documents an example of vitamin A deficiency in the developed world. We aim to provide a comprehensive description of clinical examination and multimodal imaging findings before and after vitamin supplementation for vitamin A deficiency.

Delayed Detection of Predominantly Pericentral Hydroxychloroquine Toxicity in a Dominican Patient.

Purpose: To describe delayed detection of pericentral hydroxychloroquine (HCQ) toxicity. Methods: 67-year-old Dominican woman with rheumatoid arthritis on HCQ presented for examination. Results: Spectral-domain optical coherence tomography (SD-OCT) demonstrated bilateral cystoid macular edema with parafoveal attenuation of the external limiting membrane (ELM) and the ellipsoid zone (EZ). ELM and EZ disruption was present in inferior macula. While subtle superior defects were present on 10-2 visual fields, superior pericentral defects were noted on 24-2 testing. Hyperautofluorescence along inferior arcades corresponded to SD-OCT and visual fields. Examination 2 years prior demonstrated nonspecific points of depression on 10-2 visual fields and normal central SD-OCT findings. EZ and ELM disruption was present in the perifoveal inferior macula. Conclusions: Early pericentral distribution of HCQ toxicity is not limited to Asian patients. Detecting pericentral HCQ toxicity involves reviewing entire macular cube on OCT. When OCT changes are suspected on parafoveal OCT B-scans, visual field testing with 24-2 may be more sensitive than 10-2.

Posterior Pigment Deposition as a Marker of Persistently Open Retinectomy Edge Following Retinal Detachment Repair.

Posterior pigment dispersion is a rare ophthalmic finding that has been reported in patients undergoing retinectomy with silicone oil placement and in patients who underwent significant anterior segment manipulation and vitrectomy. The pigment release is believed to occur from retinal pigment epithelium (RPE) cells in the former and the posterior iris in the latter. The exact timing of this pre-retinal pigment deposition is unknown but typically is mild and occurs over several months. A rapid progression of diffuse preretinal pigmentation is uncommon and may be suggestive of persistent RPE release from an open break or continued iris trauma with posterior pigment release. This report describes a case of profound posterior pigment deposition more than 4 months after retinectomy and oil in a patient with a persistently open retinectomy edge with anterior retinal detachment. The rapidity of pigment deposition was the clue to recognizing this subtle anterior detachment under silicone oil. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:47-49.].

An adult with COVID-19 kawasaki-like syndrome and ocular manifestations.

PURPOSE: The severe acute respiratory syndrome coronavirus-2 and its associated infection known as COVID-19 have resulted in a global pandemic. Ocular manifestations of COVID-19 are nonspecific and include hyperemia, chemosis, epiphora, secretions, and eyelid edema. There is a paucity in the literature regarding COVID-19 related inflammatory syndromes which may also include ocular manifestations. OBSERVATIONS: In pediatric patients, conjunctivitis has been recently reported in association with a multisystem inflammatory condition related to COVID-19 that shares features with Kawasaki disease and toxic shock syndrome. We describe the clinical course of an adult patient with symptoms and signs consistent with a Kawasaki-like syndrome. CONCLUSIONS AND IMPORTANCE: To our knowledge, this report may be the first case of a Kawasaki-like syndrome in an adult with COVID-19 infection.

Non-glaucoma periocular allergic, atopic, and irritant dermatitis at an academic institution: A retrospective review.

PURPOSE: To better understand the nature of periocular dermatitis (PD) patient presentation, treatment, time-to-cure, and referral pattern for allergy testing in an ophthalmic academic center. METHODS: A retrospective chart review of 344 patients diagnosed with PD between January 1, 2000 and November 30, 2016 at the Edward S. Harkness Eye Institute was performed. Eighty patients were eligible for the study. The primary endpoint was the time-to-cure. Cox proportional hazards regression was performed to assess if there was a significant difference between time-to-cure in patients treated with: 1) combination topical steroid/antibiotic (n = 6) vs. topical steroid alone (n = 40) and 2) combination topical steroid and oral antihistamine (n = 5) vs. topical steroid alone (n = 40). RESULTS: The median age of eligible patients was 57.69 years old, 66.25% of patients were female, and 41.25% had a history of atopy. Seven patients in total were referred for allergy testing. A significant difference was found in likelihood of cure when comparing combination topical steroid and oral antihistamine versus topical steroid alone, adjusting for age and gender (aHR = 3.97, 95% CI: 1.40-11.25). No significance was found when comparing combination topical steroid/antibiotic versus topical steroid alone (aHR = 1.96, 95% CI: 0.72-5.27). CONCLUSION: Patients treated with topical steroid and oral antihistamine were approximately 4 times more likely to experience cure in comparison to patients treated with topical steroids alone. While the majority of patients were not referred for formal allergy testing, this would likely be of benefit.

Low-Flow Orbital Venous Malformation Masquerading as Rhabdomyosarcoma.

A 15-month-old male was referred for biopsy of presumed rhabdomyosarcoma in the setting of rapidly progressing left-sided proptosis. Examination revealed left periorbital edema and left hypoglobus. MRI revealed a soft-tissue density mass within the left lateral retrobulbar space. Several days later, he developed acute periorbital ecchymosis and increasing edema. With high suspicion for a vascular lesion, a CT scan was performed with dynamic arterial and venous imaging. Central filling was noted in the lateral retrobulbar component with increased enhancement on delayed venous imaging in the middle cranial fossa component favoring the diagnosis of a low-flow orbital venous malformation. In the setting of spontaneous orbital hemorrhage and risk of future vision loss, the decision was made to proceed with a combined neurosurgical approach treating the intracranial component and debulking the orbital component. This case highlights the importance of thorough radiographic evaluation prior to proceeding with a surgical procedure in the appropriate clinical context.

A Simple Quantitative Measure of Orbital Compliance.

PURPOSE: This study evaluates the reliability of a frequently used subjective measurement of orbital compliance (0-3 scale) and describes a simple, quantitative measure with excellent intra- and interrater reliability. METHODS: Two examiners performed both measurements on 100 orbits (50 consecutive patients) from the office of 1 oculoplastics surgeon. Each measurement was obtained at 2 different time points, 10 minutes apart. For the subjective measurement, the patient was asked to close their eyes, and the globe was displaced posteriorly with digital pressure until moderate resistance was felt. This was graded on a 0 to 3 scale. For the quantitative measurement (millimeter scale), the difference in axial displacement was measured using a Hertel exophthalmometer. RESULTS: The subjective measurement (scale, 0-3) showed excellent test-retest reliability (average, 0.901) for both examiners at both time points and good interobserver reliability (average, 0.677). The quantitative measurement (millimeter scale) showed excellent test-retest reliability (average, 0.848) and very good interobserver reliability (average, 0.756). CONCLUSION: This study shows that while both methods have both excellent test-retest reliability, the interobserver reliability is slightly higher with the quantitative measurement. This suggests that the described measurement of orbital compliance is both a reasonable alternative and possibly more accurate measurement without the steep learning curve.

Sustained activation of ERK1/2 MAPK in Schwann cells causes corneal neurofibroma.

Recent studies have shown that constitutive activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) in Schwann cells (SCs) increases myelin thickness in transgenic mice. In this secondary analysis, we report that these transgenic mice develop a postnatal corneal neurofibroma with the loss of corneal transparency by age six months. We show that expansion of non-myelinating SCs, under the control of activated ERK1/2, also drive myofibroblast differentiation that derives from both SC precursors and resident corneal keratocytes. Further, these mice also harbor activated mast cells in the central cornea, which contributes to pathological corneal neovascularization and fibrosis. This breach of corneal avascularity and immune status is associated with the growth of the tumor pannus, resulting in a corneal stroma that is nearly four times its normal size. In corneas with advanced disease, some axons became ectopically myelinated, and the disruption of Remak bundles is evident. To determine whether myofibroblast differentiation was linked to vimentin, we examined the levels and phosphorylation status of this fibrotic biomarker. Concomitant with the early upregulation of vimentin, a serine 38-phosphorylated isoform of vimentin (pSer38vim) increased in SCs, which was attributed primarily to the soluble fraction of protein-not the cytoskeletal portion. However, the overexpressed pSer38vim became predominantly cytoskeletal with the growth of the corneal tumor. Our findings demonstrate an unrecognized function of ERK1/2 in the maintenance of corneal homeostasis, wherein its over-activation in SCs promotes corneal neurofibromas. This study is also the first report of a genetically engineered mouse that spontaneously develops a corneal tumor.

The VMAT-2 inhibitor tetrabenazine affects effort-related decision making in a progressive ratio/chow feeding choice task: reversal with antidepressant drugs.

Behavioral activation is a fundamental feature of motivation, and organisms frequently make effort-related decisions based upon evaluations of reinforcement value and response costs. Furthermore, people with major depression and other disorders often show anergia, psychomotor retardation, fatigue, and alterations in effort-related decision making. Tasks measuring effort-based decision making can be used as animal models of the motivational symptoms of depression, and the present studies characterized the effort-related effects of the vesicular monoamine transport (VMAT-2) inhibitor tetrabenazine. Tetrabenazine induces depressive symptoms in humans, and also preferentially depletes dopamine (DA). Rats were assessed using a concurrent progressive ratio (PROG)/chow feeding task, in which they can either lever press on a PROG schedule for preferred high-carbohydrate food, or approach and consume a less-preferred lab chow that is freely available in the chamber. Previous work has shown that the DA antagonist haloperidol reduced PROG work output on this task, but did not reduce chow intake, effects that differed substantially from those of reinforcer devaluation or appetite suppressant drugs. The present work demonstrated that tetrabenazine produced an effort-related shift in responding on the PROG/chow procedure, reducing lever presses, highest ratio achieved and time spent responding, but not reducing chow intake. Similar effects were produced by administration of the subtype selective DA antagonists ecopipam (D1) and eticlopride (D2), but not by the cannabinoid CB1 receptor neutral antagonist and putative appetite suppressant AM 4413, which suppressed both lever pressing and chow intake. The adenosine A2A antagonist MSX-3, the antidepressant and catecholamine uptake inhibitor bupropion, and the MAO-B inhibitor deprenyl, all reversed the impairments induced by tetrabenazine. This work demonstrates the potential utility of the PROG/chow procedure as a rodent model of the effort-related deficits observed in depressed patients.