Assessing the medical reasoning skills of GPT-4 in complex ophthalmology cases.

BACKGROUND/AIMS: This study assesses the proficiency of Generative Pre-trained Transformer (GPT)-4 in answering questions about complex clinical ophthalmology cases. METHODS: We tested GPT-4 on 422 Journal of the American Medical Association Ophthalmology Clinical Challenges, and prompted the model to determine the diagnosis (open-ended question) and identify the next-step (multiple-choice question). We generated responses using two zero-shot prompting strategies, including zero-shot plan-and-solve+ (PS+), to improve the reasoning of the model. We compared the best-performing model to human graders in a benchmarking effort. RESULTS: Using PS+ prompting, GPT-4 achieved mean accuracies of 48.0% (95% CI (43.1% to 52.9%)) and 63.0% (95% CI (58.2% to 67.6%)) in diagnosis and next step, respectively. Next-step accuracy did not significantly differ by subspecialty (p=0.44). However, diagnostic accuracy in pathology and tumours was significantly higher than in uveitis (p=0.027). When the diagnosis was accurate, 75.2% (95% CI (68.6% to 80.9%)) of the next steps were correct. Conversely, when the diagnosis was incorrect, 50.2% (95% CI (43.8% to 56.6%)) of the next steps were accurate. The next step was three times more likely to be accurate when the initial diagnosis was correct (p<0.001). No significant differences were observed in diagnostic accuracy and decision-making between board-certified ophthalmologists and GPT-4. Among trainees, senior residents outperformed GPT-4 in diagnostic accuracy (p≤0.001 and 0.049) and in accuracy of next step (p=0.002 and 0.020). CONCLUSION: Improved prompting enhances GPT-4's performance in complex clinical situations, although it does not surpass ophthalmology trainees in our context. Specialised large language models hold promise for future assistance in medical decision-making and diagnosis.

The role of optical coherence tomography angiography in dome-shaped maculopathy.

PURPOSE: To demonstrate the role of optical coherence tomography angiography (OCT-A) in the management of dome-shaped maculopathy (DSM). METHODS: Retrospective case review. RESULTS: A 52-year-old woman was referred to our retina service for potential bilateral choroidal neovascular membrane (CNVM) and blurry vision bilaterally. Initial spectacle-corrected visual acuity (VA) was 20/30-2 in the right eye (RE) and 20/30+2 in the left eye (LE). DSM was diagnosed on OCT. In both eyes, OCT B-scan passing through the fovea showed shallow, irregular RPE elevation (SIRE) suspicious of occult (type 1) CNVM. The outer retina and choriocapillaris angiograms showed a zone of nonexudative CNVM in the RE and exudative CNVM in the LE. Given the persistent SRF with CNVM in the LE, we elected to perform intravitreal injections of ranibizumab 0.5 mg on a treat and extend regimen. Upon the most recent follow-up, the best corrected VA improved to 20/20 in the LE with no persisting SRF. CONCLUSION: We present a case where assessing disease progression, the development of CNVM and evaluating the efficiency of therapies were realized through the application of novel OCT-A technology. This diagnostic tool may be used to guide clinicians in their management of DSM, as demonstrated through our experience. OCT-A can also make it possible to visualize nonexudative CNVM lesions that may be missed on traditional imaging assessments.

Paracentral Acute Middle Maculopathy in Migraines with Aura.

Paracentral acute middle maculopathy (PAMM) has recently been described following episodes of migraine. In this report, we present a case of PAMM and describe the role of en face optical coherence tomography (OCT). A 75-year-old woman presented with subjective vision loss over a 2-week period in the right eye. She was known for migraines with aura that presented with progressive spreading of positive and negative visual phenomena which usually resolved in under an hour. Her recent migraine episode was "atypical," as it lasted 3 days. She also experienced a monocular central scotoma with "black spots and jagged, zig-zag edges." The positive auras resolved spontaneously, whereas the central scotoma persisted. Spectral domain OCT showed an area of perifoveal hyperreflectivity from the inner plexiform to the outer plexiform layers consistent with PAMM. The mid-retina en face OCT and OCT angiography demonstrated an ovoid focal patch of hyperreflectivity with flow interruption, characteristic of globular PAMM. We diagnosed her with migraines with aura and presumed retinal vasospasm, complicated by retinal ischemia in the form of globular PAMM. Acute retinal ischemia, which may require urgent neurovascular workup and giant cell arteritis evaluation, must be considered in patients with migraines alongside persistent visual changes. Diagnosing PAMM requires a high level of suspicion since it can present without significant changes in visual acuity, visual fields, and fundus photographs. With the inclusion of en face OCT in the clinicians' diagnostic armamentarium, the slightest signs of retinal ischemic changes, such as PAMM, become evident.

Correlation of clinical response with homocysteine reduction during therapy with reduced B vitamins in patients with MDD who are positive for MTHFR C677T or A1298C polymorphism: a randomized, double-blind, placebo-controlled study.

OBJECTIVE: This study was designed to evaluate the efficacy and safety of reduced B vitamins as monotherapy in adults with major depressive disorder (MDD) who were also positive for at least 1 methylenetetrahydrofolate reductase (MTHFR) polymorphism associated with depression and further test the hypothesis that reduced (metabolized) B vitamins will lower homocysteine in a majority of clinically responding patients. METHODS: 330 adult patients with MDD (DSM-5) and positive for either MTHFR C677T or A1298C polymorphism were enrolled in a trial conducted between August 1, 2014, and April 3, 2015. 160 patients received placebo, while 170 received a capsule containing a combination of reduced B vitamins. Plasma homocysteine levels were measured at baseline and week 8. The Montgomery-Asberg Depression Rating Scale (MADRS) was used to evaluate efficacy for MDD. RESULTS: 159 of 170 vitamin-treated patients and 123 of 160 placebo-treated patients were completers. Of the active treatment group, 131 (82.4%) showed a reduction in homocysteine (for a mean in this subgroup of 25%, P < .001), while 28 (17.6%) showed no significant change. Placebo patients demonstrated a small elevation in homocysteine. Active-treatment patients demonstrated, on average, a 12-point reduction on the MADRS by week 8, and 42% achieved full remission (P < .001). No side effect was significantly different between groups. No patients experienced mania. CONCLUSIONS: A combination of reduced B vitamins and micronutrients, when used in the treatment of MDD in patients with MTHFR polymorphism, resulted in a separation from placebo by week 2, and 42% of the treatment arm achieved remission by week 8. Further, clinical improvement correlated with a significant reduction in homocysteine levels in a majority of responders. These results support the homocysteine theory of depression and the safety and therapeutic benefit of reduced B vitamins as monotherapy for MDD, particularly in patients with MTHFR polymorphism. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02709668.

The role of L-methylfolate in depressive disorders.

Major depressive disorder (MDD) is a debilitating and often recurrent illness. An initial antidepressant trial is effective at achieving remission for approximately 30% of patients when prescribed as monotherapy, with the majority of patients returning as partial or non-responders. Switching antidepressants or adding augmentation agents are standard therapeutic options used to achieve and maintain remission. Suboptimal serum and red blood cell folate levels have been associated with a poorer response to antidepressant therapy, a greater severity of symptoms, later onset of clinical improvement, and overall treatment resistance. This Expert Review Supplement reviews the evidence for L-methylfolate as an augmentation agent in depression and discusses its clinical use elaborated by three clinical presentations.

Atypicality of atypical antipsychotics.

OBJECTIVE: To review the current definition of atypicality, discuss the unique features of each atypical antipsychotic, and determine whether the available drugs in this class really meet the classical definition of atypicality. DATA SOURCES: A PubMed search was conducted to identify literature on the subject of this review, supported by additional articles based on the author's clinical knowledge and experience. STUDY SELECTION AND DATA EXTRACTION: Relevant references were extracted and summarized in order to meet the objective of the article. DATA SYNTHESIS: Atypical antipsychotics are considered a major advance over conventional antipsychotics, primarily because they offer effective treatment alternatives that are relatively free of extrapyramidal symptoms. In fact, the term atypicality was originally used to describe antipsychotic agents with a minimal risk of causing extrapyramidal symptoms. However, over the years the definition has been modified such that there is currently no consensus on a true definition of atypicality for these agents. Each of the atypical antipsychotics (clozapine, risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole) commercially available in the United States is unique in terms of its pharmacologic profile, differing with respect to receptor-binding affinity, mechanism of action, and adverse events. Of the available atypical antipsychotics, clozapine and quetiapine have shown the lowest propensity to cause extrapyramidal symptoms. Although the risk of extra-pyramidal symptoms is lower with risperidone and olanzapine than with conventional antipsychotics, risk increases with dose escalation. Data for ziprasidone indicate that the risk of extrapyramidal symptoms may be similar to that of risperidone and olanzapine. There is a concern of akathisia with aripiprazole; however, more experience with this agent is needed before definitive conclusions are made. CONCLUSION: If the definition of "atypical" antipsychotic is considered to be freedom from extrapyramidal symptoms, then, based on a comprehensive review of available data and clinical experience, clozapine and quetiapine appear to be the only true atypicals.