ADAPTIVE OPTICS AND MULTIMODAL IMAGING FOR INFLAMMATORY VITREORETINAL INTERFACE ABNORMALITIES.

PURPOSE: To investigate changes to the vitreoretinal interface in uveitis with multimodal imaging including adaptive optics. METHODS: Four eyes (four patients) affected by fovea-attached (subtype 1A) or fovea-sparing epiretinal membranes (ERMs) on spectral-domain optical coherence tomography or visible internal limiting membrane (ILM) on infrared scanning laser ophthalmoscope (SLO) fundus imaging were recruited in this pilot study. The microstructure of the vitreoretinal interface was imaged using flood-illumination adaptive optics (FIAO), and the images were compared with the cross-sectional spectral-domain optical coherence tomography data. RESULTS: Adaptive optics images revealed multiple abnormalities of the vitreoretinal interface, such as deep linear striae in ERM, and hyperreflective microstructures at the location of ERMs and ILMs. The cone mosaic was imaged by FIAO and was found altered in the four eyes with ERMs or visible ILM. The same four eyes presented alteration of photopic 30 Hz flicker that was reduced in amplitude indicating cone inner retinal layer dysfunction. CONCLUSION: FIAO imaging can identify specific patterns associated with ERMs and ILMs. Correlating FIAO imaging of the vitreomacular interface with the structural alterations seen in FIAO at the level of the outer retinal structures can help understand the cause of significant macular dysfunction associated with ERM.

ChatGPT and Beyond: An overview of the growing field of large language models and their use in ophthalmology.

ChatGPT, an artificial intelligence (AI) chatbot built on large language models (LLMs), has rapidly gained popularity. The benefits and limitations of this transformative technology have been discussed across various fields, including medicine. The widespread availability of ChatGPT has enabled clinicians to study how these tools could be used for a variety of tasks such as generating differential diagnosis lists, organizing patient notes, and synthesizing literature for scientific research. LLMs have shown promising capabilities in ophthalmology by performing well on the Ophthalmic Knowledge Assessment Program, providing fairly accurate responses to questions about retinal diseases, and in generating differential diagnoses list. There are current limitations to this technology, including the propensity of LLMs to "hallucinate", or confidently generate false information; their potential role in perpetuating biases in medicine; and the challenges in incorporating LLMs into research without allowing "AI-plagiarism" or publication of false information. In this paper, we provide a balanced overview of what LLMs are and introduce some of the LLMs that have been generated in the past few years. We discuss recent literature evaluating the role of these language models in medicine with a focus on ChatGPT. The field of AI is fast-paced, and new applications based on LLMs are being generated rapidly; therefore, it is important for ophthalmologists to be aware of how this technology works and how it may impact patient care. Here, we discuss the benefits, limitations, and future advancements of LLMs in patient care and research.

Pulsatile microvascular cerebral blood flow waveforms change with intracranial compliance and age.

Significance: Diffuse correlation spectroscopy (DCS) is an optical method to measure relative changes in cerebral blood flow (rCBF) in the microvasculature. Each heartbeat generates a pulsatile signal with distinct morphological features that we hypothesized to be related to intracranial compliance (ICC). Aim: We aim to study how three features of the pulsatile rCBF waveforms: the augmentation index (AIx), the pulsatility index, and the area under the curve, change with respect to ICC. We describe ICC as a combination of vascular compliance and extravascular compliance. Approach: Since patients with Chiari malformations (CM) (n=30) have been shown to have altered extravascular compliance, we compare the morphology of rCBF waveforms in CM patients with age-matched healthy control (n=30). Results: AIx measured in the supine position was significantly less in patients with CM compared to healthy controls (p<0.05). Since physiologic aging also leads to changes in vessel stiffness and intravascular compliance, we evaluate how the rCBF waveform changes with respect to age and find that the AIx feature was strongly correlated with age (Rhealthy subjects=-0.63, Rpreoperative CM patient=-0.70, and Rpostoperative CM patients=-0.62, p<0.01). Conclusions: These results suggest that the AIx measured in the cerebral microvasculature using DCS may be correlated to changes in ICC.

Novel pharmaceuticals for the management of retinal vein occlusion and linked disorders.

INTRODUCTION: Retinal vein occlusion (RVO) is the second leading cause of blindness from retinal vascular disease behind diabetic retinopathy. Anti-vascular endothelial growth factor (VEGF) and glucocorticoid therapy are the cornerstones of pharmaceutical treatment for RVO. There is considerable interest in developing new pharmaceuticals in and out of these two classes to reduce costs, lower injection burden, and treat the occlusion itself, rather than the complications. AREAS COVERED: In this review, we discuss novel pharmaceuticals for the treatment of RVO outside of current standard of care. We performed a comprehensive literature search encompassing pharmaceuticals that have recently been approved or have shown promising results in early clinical trials or animal models. EXPERT OPINION: Anti-VEGF therapy remains the most efficacious treatment for RVO with a very favorable side effect profile. New biosimilars reduce costs while maintaining efficacy. Novel glucocorticoids may be a useful therapy in patients for whom anti-VEGF therapy has failed, or as an adjunct. Pharmaceuticals in other drug classes, particularly those with neuroprotective or regenerative properties, as well as those geared toward treating the occlusion itself, represent exciting options for early RVO therapy, but are likely years away from clinical relevance.

The full range of ophthalmological clinical manifestations in systemic lupus erythematosus.

Purpose: To determine the full range of ophthalmological clinical manifestations in systemic lupus erythematosus (SLE) and to compare the systemic features associated with them. Methods: Files of 13 patients with ocular SLE (n = 20 eyes) diagnosed as per the American College of Rheumatology (ACR) 2012 revised criteria were retrospectively reviewed. Results: The following clinical manifestations were found: keratoconjunctivitis sicca (n = three patients), anterior uveitis associated with an inflammatory pseudo-tumor orbital mass (n = one patient, one eye), episcleritis and periorbital edema (n = one patient, two eyes), posterior scleritis (n = one patient, two eyes), bilateral papillary edema in the context of idiopathic intracranial hypertension (n = one patient, one eye), inflammatory optic neuritis (n = one patient, one eye), and lupus retinopathies with varying degrees of capillary occlusions mainly arteriolar (n = seven patients, 13 eyes) and larger arteries or veins (retinal arteries occlusions and retinal veins occlusions) (n = one patient, two eyes). Some patients presented with combined ophthalmological manifestations.Systemic SLE was discovered by its ophthalmic manifestation in three cases (23%) and was previously known in the other 10 cases (77%). On average, ocular symptoms were seen 8 years after the initial diagnosis of SLE. Other systemic SLE disorders included cutaneous disorders (77%), joint disorders (38%), central nervous system (CNS) disorders (23%), renal disorders (38%), and oral ulcers (23%).Treatment of the ophthalmic system manifestations of lupus included local steroid therapies along with systemic immunosuppression.The most common laboratory ACR criteria were: high levels of antinuclear antibodies (ANA) (100%), positive anti-Sm (64%), anti-dsDNA (27%), low complement levels (27%), and positive antiphospholipid (APL) antibodies (18%). Discussion: SLE activity in the ophthalmic system is characterized by its functional severity and the range of involvement can be categorized by anatomical involvement: presence of anterior uveitis, episcleritis, scleritis, periorbital edema, posterior uveitis with retinal vascular ischemia, or papillary edema. Not currently part of the diagnosis criteria of the SLE ACR given its rarity, the ocular localization of the pathology led to the diagnosis of SLE in three cases; thus, developing a greater understanding of ocular lupus may help in identifying and treating systemic manifestations of lupus earlier.

3-D printed photoreceptor phantoms for evaluating lateral resolution of adaptive optics imaging systems.

With adaptive optics (AO), optical coherence tomography and scanning laser ophthalmoscopy imaging systems can resolve individual photoreceptor cells in living eyes, due to enhanced lateral spatial resolution. However, no standard test method exists for experimentally quantifying this parameter in ophthalmic AO imagers. Here, we present three-dimensional (3-D) printed phantoms, which enable the measurement of lateral resolution in an anatomically relevant manner. We used two-photon polymerization to fabricate two phantoms, which mimic the mosaic of cone photoreceptor outer segments at multiple retinal eccentricities. With these phantoms, we demonstrated that the resolution of two multimodal AO systems is similar to theoretical predictions, with some intriguing speckle effects.