Large language models approach expert-level clinical knowledge and reasoning in ophthalmology: A head-to-head cross-sectional study.

Large language models (LLMs) underlie remarkable recent advanced in natural language processing, and they are beginning to be applied in clinical contexts. We aimed to evaluate the clinical potential of state-of-the-art LLMs in ophthalmology using a more robust benchmark than raw examination scores. We trialled GPT-3.5 and GPT-4 on 347 ophthalmology questions before GPT-3.5, GPT-4, PaLM 2, LLaMA, expert ophthalmologists, and doctors in training were trialled on a mock examination of 87 questions. Performance was analysed with respect to question subject and type (first order recall and higher order reasoning). Masked ophthalmologists graded the accuracy, relevance, and overall preference of GPT-3.5 and GPT-4 responses to the same questions. The performance of GPT-4 (69%) was superior to GPT-3.5 (48%), LLaMA (32%), and PaLM 2 (56%). GPT-4 compared favourably with expert ophthalmologists (median 76%, range 64-90%), ophthalmology trainees (median 59%, range 57-63%), and unspecialised junior doctors (median 43%, range 41-44%). Low agreement between LLMs and doctors reflected idiosyncratic differences in knowledge and reasoning with overall consistency across subjects and types (p>0.05). All ophthalmologists preferred GPT-4 responses over GPT-3.5 and rated the accuracy and relevance of GPT-4 as higher (p<0.05). LLMs are approaching expert-level knowledge and reasoning skills in ophthalmology. In view of the comparable or superior performance to trainee-grade ophthalmologists and unspecialised junior doctors, state-of-the-art LLMs such as GPT-4 may provide useful medical advice and assistance where access to expert ophthalmologists is limited. Clinical benchmarks provide useful assays of LLM capabilities in healthcare before clinical trials can be designed and conducted.

Molecular and Phenotypic Characterization of Ocular Methicillin-Resistant Staphylococcus epidermidis Isolates in Taiwan.

Purpose: Staphylococcus epidermidis, a commensal, has emerged as an important opportunistic pathogen, particularly methicillin-resistant S. epidermidis (MRSE). The mechanism behind this transformation remains unclear. This study aimed to investigate the molecular and phenotypic characteristics of MRSE isolated from healthy conjunctiva and ocular infections. Methods: We collected MRSE isolates from two groups: healthy conjunctiva from patients undergoing cataract surgeries and ocular infections at our hospital. Genotypic analysis included pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), staphylococcal cassette chromosome mec (SCCmec), and biofilm-related genes (icaA, aap, and bhp). Additionally, phenotypic data on biofilm production and antibiotic susceptibility were recorded. Results: A total of 86 isolates, including 42 from healthy conjunctiva and 44 from ocular infections, were analyzed. MLST identified 21 sequence types (STs), with ST59 being the most frequent (n = 33, 39.5%), followed by ST130 (n = 10, 11.6%), ST57 (n = 6, 7.0%), and ST2 (n = 6, 7.0%). All isolates were categorized in 23 PFGE types, and SCCmec IV was the most prevalent SCCmec type (n = 52, 60.5%). The two sources of isolates exhibited overlapping molecular types and phenotypic traits, although the ocular infection isolates exhibited significantly higher multidrug resistance compared to healthy conjunctiva isolates (P = 0.032). When contrasting ST59 with non-ST59, ST59 displayed a significantly higher presence of aap (100%) and bhp (69.7%) while lacking icaA (0%). ST59 also showed lower susceptibility to fluoroquinolones compared to non-ST59 (42.4%-54.5% vs. 75.5%-83.0%; P < 0.01). Conclusions: MRSE isolates from healthy conjunctiva and ocular infections demonstrated a degree of resemblance. Specific strains, notably ST59, exhibited distinctive characterizations.

Optical Coherence Tomography and Optical Coherence Tomography Angiography in Pediatric Retinal Diseases.

Indirect ophthalmoscopy and handheld retinal imaging are the most common and traditional modalities for the evaluation and documentation of the pediatric fundus, especially for pre-verbal children. Optical coherence tomography (OCT) allows for in vivo visualization that resembles histology, and optical coherence tomography angiography (OCTA) allows for non-invasive depth-resolved imaging of the retinal vasculature. Both OCT and OCTA were extensively used and studied in adults, but not in children. The advent of prototype handheld OCT and OCTA have allowed for detailed imaging in younger infants and even neonates in the neonatal care intensive unit with retinopathy of prematurity (ROP). In this review, we discuss the use of OCTA and OCTA in various pediatric retinal diseases, including ROP, familial exudative vitreoretinopathy (FEVR), Coats disease and other less common diseases. For example, handheld portable OCT was shown to detect subclinical macular edema and incomplete foveal development in ROP, as well as subretinal exudation and fibrosis in Coats disease. Some challenges in the pediatric age group include the lack of a normative database and the difficulty in image registration for longitudinal comparison. We believe that technological improvements in the use of OCT and OCTA will improve our understanding and care of pediatric retina patients in the future.

Maternal mosaicism in SSBP1 causing optic atrophy with retinal degeneration: implications for genetic counseling.

BACKGROUND: Optic atrophy-13 with retinal and foveal abnormalities (OPA13) (MIM #165510) is a mitochondrial disease in which apparent bilateral optic atrophy is present and sometimes followed by retinal pigmentary changes or photoreceptors degeneration. OPA13 is caused by heterozygous mutation in the SSBP1 gene, associated with variable mitochondrial dysfunctions. RESULTS: We have previously reported a 16-year-old Taiwanese male diagnosed with OPA13 and SSBP1 variant c.320G>A (p.Arg107Gln) was identified by whole exon sequence (WES). This variant was assumed to be de novo since his parents were clinically unaffected. However, WES and Sanger sequencing further revealed the proband's unaffected mother carrying the same SSBP1 variant with a 13% variant allele frequency (VAF) in her peripheral blood. That finding strongly indicates the maternal gonosomal mosaicism contributing to OPA13, which has not been reported before. CONCLUSIONS: In summary, we described the first case of OPA13 caused by maternal gonosomal mosaicism in SSBP1. Parental mosaicism could be a serious issue in OPA13 diagnosis, and appropriate genetic counseling should be considered.

Maternal Mosaicism in SSBP1 Causing Optic Atrophy with Retinal Degeneration: Implications for Genetic Counseling.

Background: Optic atrophy-13 with retinal and foveal abnormalities (OPA13) (MIM #165510) is a mitochondrial disease in which apparent bilateral optic atrophy is present and sometimes followed by retinal pigmentary changes or photoreceptors degeneration. OPA13 is caused by heterozygous mutation in the SSBP1 gene, associated with variable mitochondrial dysfunctions. Results: We have previously reported a 16-year-old Taiwanese male diagnosed with OPA13 and SSBP1 variant c.320G>A (p.Arg107Gln) was identified by whole exon sequence (WES). This variant was assumed to be de novo since his parents were clinically unaffected. However, WES and Sanger sequencing further revealed the proband’s unaffected mother carrying the same SSBP1 variant with a 13% variant allele frequency (VAF) in her peripheral blood. That finding strongly indicates the maternal gonosomal mosaicism contributing to OPA13, which has not been reported before. Conclusions: In summary, we described the first case of OPA13 caused by maternal gonosomal mosaicism in SSBP1 . Parental mosaicism could be a serious issue in OPA13 diagnosis, and appropriate genetic counseling should be considered.

Congenital Stationary Night Blindness: Clinical and Genetic Features.

Congenital stationary night blindness (CSNB) is an inherited retinal disease (IRD) that causes night blindness in childhood with heterogeneous genetic, electrophysical, and clinical characteristics. The development of sequencing technologies and gene therapy have increased the ease and urgency of diagnosing IRDs. This study describes seven Taiwanese patients from six unrelated families examined at a tertiary referral center, diagnosed with CSNB, and confirmed by genetic testing. Complete ophthalmic exams included best corrected visual acuity, retinal imaging, and an electroretinogram. The effects of identified novel variants were predicted using clinical details, protein prediction tools, and conservation scores. One patient had an autosomal dominant CSNB with a RHO variant; five patients had complete CSNB with variants in GRM6, TRPM1, and NYX; and one patient had incomplete CSNB with variants in CACNA1F. The patients had Riggs and Schubert-Bornschein types of CSNB with autosomal dominant, autosomal recessive, and X-linked inheritance patterns. This is the first report of CSNB patients in Taiwan with confirmed genetic testing, providing novel perspectives on molecular etiology and genotype-phenotype correlation of CSNB. Particularly, variants in TRPM1, NYX, and CACNA1F in our patient cohort have not previously been described, although their clinical significance needs further study. Additional study is needed for the genotype-phenotype correlation of different mutations causing CSNB. In addition to genetic etiology, the future of gene therapy for CSNB patients is reviewed and discussed.

Foveal hypoplasia and characteristics of optical components in patients with familial exudative vitreoretinopathy and retinopathy of prematurity.

There has been limited research regarding the status of foveal hypoplasia and the characteristics of the optical components of the eye in patients with familial exudative vitreoretinopathy (FEVR) and retinopathy of prematurity (ROP). In this retrospective cohort study, patients were classified into five groups: patients with stage 1 and 2 FEVR (FEVR group), patients with ROP who received treatment (treated ROP group), patients with ROP who did not receive treatment (untreated ROP group), patients without ROP who had been born preterm (preterm group), and healthy patients who had been born at term (full-term group). Visual acuity, refractive error, characteristics of the optical components, and features of the fovea were compared. In total, 179 eyes from 100 patients were included. Patients in the FEVR group had the highest degrees of myopia (p < 0.001). The axial length of patients in the FEVR group was significantly longer than that of patients in the treated and untreated ROP, preterm, and full-term groups (p < 0.001, p < 0.001, p = 0.001, and p = 0.003, respectively). Patients in the FEVR group had a higher proportion of grade 4 foveal hypoplasia and thinner foveae than those in the other groups (p < 0.001). Patients with FEVR had significantly greater myopic change than patients with ROP; the significantly longer axial length of the FEVR group might be the reason for the greater myopic change and lesser macular thickness. Patients in the FEVR group had more foveal hypoplasia than those in the other groups.

Photoreceptor Manifestations of Primary Mitochondrial Optic Nerve Disorders.

Purpose: To compare the manifestations of photoreceptors (PRs) in three hereditary optic neuropathies affected by primary mitochondrial dysfunction and discuss whether the retinal ganglion cells (RGCs) or the PRs are preferentially affected. Methods: A retrospective analysis of patients with genetically confirmed diagnoses of optic neuropathies associated with mitochondrial dysfunction was performed. This cohort included Leber's hereditary optic neuropathy (LHON), autosomal dominant optic atrophy type 1 (OPA1), and optic atrophy type 13 (OPA13). Patient chart evaluations included clinical characteristics, best-corrected visual acuity (BCVA), fundus photography, spectral-domain optical coherence tomography (SD-OCT), electroretinogram (ERG), and visual evoked potential data. Results: This analysis included seven patients with LHON, six with OPA1, and one with OPA13 from a tertiary medical center. Thirteen of the 14 individuals were male. The average BCVA at diagnosis was 20/285 and 20/500 in the right and left eyes, respectively. Five of the seven patients with LHON, and three of the six patients with OPA1 also showed a mild amplitude reduction or delayed latency on light-adapted ERG and 30-Hz flicker responses; however, SD-OCT imaging did not show correlated PR abnormalities. Notably, a 7-year follow-up of a patient with OPA13 revealed degeneration of RGCs prior to the degeneration of PRs. Follow-up data also demonstrated continuous loss of cone outer segment tips on SD-OCT imaging. Conclusions: RGCs are, in general, affected by mitochondrial dysfunction, whereas variable PR dysfunction exists in patients with LHON and OPA1, especially with respect to the cone responses. Involvement of PRs is particularly evident in OPA13 after RGC degenerations.

Comparison of risks of arterial thromboembolic events and glaucoma with ranibizumab and aflibercept intravitreous injection: A nationwide population-based cohort study.

BACKGROUND: To compare intravitreal aflibercept injection with intravitreal ranibizumab injection for the risk of major arterial thromboembolic events (ATEs) and glaucoma. METHODS: This retrospective, nationwide cohort study investigated 15 611 and 3867 patients aged >50 years with at least one pharmacy claim for intravitreal ranibizumab injection and aflibercept injection between 2011 and 2016, respectively. The inverse probability of treatment weighting method was performed to adjust the baseline difference between the two groups and the hazard risk of adverse events was estimated using the Cox proportional regression model. RESULTS: No significant difference was noted between intravitreal ranibizumab and aflibercept injection for arterial thromboembolic risk, including ischemic stroke and acute myocardial infarction, during a 2-year follow-up (adjusted hazard ratio (HR): 0.87, 95% confidence interval (CI): 0.53-1.42; P = .583). Subgroup analyses revealed that patients age >65 years (adjusted HR: 0.64, 95% CI: 0.45-0.92) and those without coronary artery disease (adjusted HR: 0.59, 95% CI: 0.37-0.95) had significantly lower arterial thromboembolic risk in the aflibercept group than in the ranibizumab group. Additionally, the risk of glaucoma development after intravitreal injection did not significantly differ between the two groups (adjusted HR: 0.63, 95% CI: 0.37-1.06; P = .084). CONCLUSIONS: No significant differences in the risk of major ATEs and glaucoma were found between ranibizumab and aflibercept, and aflibercept might be safe for use in elderly patients.

Postvitrectomy endophthalmitis caused by Morganella morganii: a case report and literature review.

BACKGROUND: Postvitrectomy endophthalmitis is a rare and serious complication following vitreoretinal surgeries. Morganella morganii, an emerging gram-negative, facultative anaerobic rod, is related to severe nosocomial infections in various organs and thus has gained importance in recent decades. Morganella morganii infection following intraocular surgery is rarely reported. CASE PRESENTATION: We report an immunocompetent patient with Morganella morganii-related endophthalmitis after vitrectomy for retinal detachment who presented with hand motion visual acuity, hypopyon and a unique retrolental exudative membrane. Initially, the patient was unresponsive to empirical intravitreal ceftazidime and vancomycin but recovered with vision preservation (20/63) after surgical removal of the membrane and silicone oil tamponade. CONCLUSIONS: Morganella morganii intraocular infection is often devastating, likely due to its high multidrug-resistance rate via intrinsic ß-lactamase production, multiple acquired traits related to additional genetic mechanisms, and fimbrial adhesion, urease production, and type III secretion system-associated biofilm formation. The above characteristics of M. morganii may lead to an inadequate response to empirical intravitreal antibiotics, and early surgical intervention should be considered.

Prediction of residual astigmatism in cataract surgery at different diameter zones using optical biometry measurement.

The studies for astigmatism prediction error at different diameters using optical biometry are scant. We investigated patients who underwent cataract surgery with monofocal, nontoric intraocular lens (IOL) from 2017 through 2019 in a medical center. Patients with prior refractive surgeries, corneal opacity, or surgical complications were excluded. Corneal astigmatism (CA) was measured using AL-Scan at 2.4- and 3.3-mm diameter zones and calculated using the Barrett toric calculator preoperatively and postoperatively. The mean absolute error and centroid prediction error for the two zones were computed using double-angle plots. In total, 101 eyes of 76 patients were analyzed. Mean patient age was 68.7 ± 9.3 years and mean preoperative CA power was 0.7 ± 0.5 D. The overall centroid prediction error a 3.3 mm (0.09 ± 0.58 D@25) was significantly lower than that at 2.4 mm (0.09 ± 0.68 D@87) on the X-axis (P = 0.003). The 3.3-mm measurement also had a lower centroid prediction error than the 2.4-mm did for eyes with against-the-rule (ATR) and oblique astigmatism (P = 0.024; 0.002 on X-axis, respectively). The 3.3-mm measurement provided a more accurate CA estimation than the 2.4-mm did, particularly for ATR astigmatism. Diameter zone and astigmatism type should be considered crucial to precise astigmatism calculation.

Outcomes and longitudinal trend of traumatic cataract wound dehiscence in patients with blunt ocular injury.

Longitudinal trends on traumatic cataract wound dehiscence are scant. In this study, we present the characteristics of traumatic cataract wound dehiscence using 15 years of longitudinal trend in one of the largest medical centers in Taiwan for a period when cataract surgeries were gradually shifting from extracapsular cataract extraction (ECCE) to phacoemulsification. All patients with a prior cataract surgery who suffered from blunt open globe trauma between 2001 and 2015 at a tertiary referral center in Taiwan were included. The number of cases per year; type of prior cataract surgery; visual acuity (VA); mechanism and place of injury were analyzed. The risk factors associated with final VA were investigated in patients followed up for ≥ 1 month. Seventy-six eyes of 75 patients were included and all of them were traumatic cataract wound dehiscence with a prior ECCE (65 eyes) or phacoemulsification. The most common mechanism and place of injury was fall and at home in both cataract surgical types. The mean log of the minimal angle resolution (logMAR) of final VA was 2.15 ± 0.88 (ECCE) and 1.61 ± 0.83 (phacoemulsification) (P = .026). The most significant risk factors associated with worse final VA were retinal detachment at the initial visit and low ocular trauma score (both P < .001). Long-term visual outcome of phacoemulsification wound dehiscence was better than that of ECCE wound after a blunt trauma.

Late spontaneous bilateral intraocular lens subluxation accompanied with intraocular pressure elevation in a patient with acromegaly.

A 53-year-old male with newly diagnosed acromegaly came to our clinic with the chief complaint of diplopia. He had the past ocular history of uneventful phacoemulsification cataract surgery with intraocular lens (IOL) implantation in the right eye 17 years ago and left eye 15 years ago. Postoperative examination showed remarkable improvement in visual acuity. Two years ago, he developed elevated intraocular pressure (IOP) in both eyes, which was well-controlled with the use of travoprost 0.004%/timolol 0.5%. At the clinic, slit-lamp examination revealed inferiorly subluxated IOL bilaterally. The patient received IOL repositioning with pars plana vitrectomy and scleral fixation in the left eye smoothly. We hypothesize that excess growth hormone is associated with dysregulation of fibrillin, resulting in zonular weakness, which causes late bilateral IOL subluxation. Elevated IOP may also be related to acromegaly. To the best of our knowledge, this is the first report to describe the association between IOL subluxation and acromegaly.

Hydrocele in recurrent acute pancreatitis caused by testicular venous obstruction: A case report of a rare complication (CARE-compliant).

RATIONALE: Scrotal swelling is a rare complication of acute pancreatitis. It had been explained by fluid accumulation in scrotum originated from abdomen. Here we demonstrated a case of recurrent pancreatitis with hydrocele caused by impaired testicular venous drainage. PATIENT CONCERNS: A 53-year-old man presented with sudden onset epigastric pain after an alcohol binge. Recurrent acute pancreatitis was confirmed by medical history, physical examination, elevated lipase level and abdominal computed tomography (CT) scan. Right scrotal swelling was noticed on the next day. DIAGNOSIS: The scrotal ultrasonography demonstrated fluid accumulation around the testis and varicocele consistent with scrotal hydrocele. CT scans of the abdomen and pelvis showed encasement of the right testicular vein by pancreatic phlegmon. INTERVENTIONS: The patient was subject to Nulla per os, hydration, and opioid analgesics for pancreatitis. No intervention was performed for scrotal swelling. OUTCOMES: Hydrocele gradually resolved along with acute pancreatitis. LESSONS: Pancreatic phlegmon compromised testicular venous return which led to scrotal hydrocele and posed a threat to fertility. The study has provided a novel pathologic linkage. This complication should be taken into account.

Effectiveness of corticosteroids versus adrenocorticotropic hormone for infantile spasms: a systematic review and meta-analysis.

OBJECTIVE: To compare the therapeutic effectiveness of oral corticosteroids with that of adrenocorticotrophic hormone for infantile spasms. METHODS: PubMed, Embase, Scopus, and the Cochrane library were searched to retrieve studies published before December 2018 to identify pediatric patients with a diagnosis of infantile spasms. The interventions of oral corticosteroids and adrenocorticotrophic hormone were compared. We included only randomized controlled trials that reported the cessation of spasms as treatment response. The primary outcome was clinical spasm cessation on day 13 or 14. The secondary outcomes were the resolution of hypsarrhythmia, side effects, continued spasm control, spasm relapse rate, and subsequent epilepsy rate. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, the study-level quality assessment was conducted using the Cochrane risk-of-bias tool. RESULTS: After extensive review, 39 articles were included for meticulous evaluation. Five randomized controlled trials with a total of 239 individuals were eligible for further analysis. No significant difference was detected between the corticosteroids and adrenocorticotrophic hormone in the cessation of clinical spasms (odds ratio [OR]: 0.54; 95% confidence interval [CI]: 0.16 to 1.81; P = 0.32). The subgroups of high-dose prednisolone versus adrenocorticotrophic hormone and low-dose prednisone versus adrenocorticotrophic hormone also exhibited no significant difference. Furthermore, the two subgroups did not differ in terms of hypsarrhythmia resolution, side effects, relapse rate, or subsequent epilepsy rate. INTERPRETATION: This meta-analysis suggests that high-dose prednisolone is not inferior to adrenocorticotrophic hormone and that it be considered a safe and effective alternative treatment.