OBJECTIVE: Train an automatic retinal image analysis (ARIA) method to screen glaucomatous optic neuropathy (GON) on non-mydriatic retinal images labelled with the additional results of optical coherence tomography (OCT) and assess different models for the GON classification.
METHODS: All the images were obtained from the hospital for training and 10-fold cross-validation. Two methods were used to improve the classification performance: (1) using images labelled with the additional results of OCT as the reference standard and (2) generating models using retinal features from the entire images, the region of interest (ROI) of the optic disc, and the ROI of the macula, and the combination of all the features.
RESULTS: Overall, we collected 1338 images with paired OCT scans. In 10-fold validation, ARIA achieved sensitivities of 92.2 %, 92.7% and 85.7%, specificities of 88.8%, 86.7% and 80.2% and accuracies of 90.6%, 89.9% and 83.1% using the retinal features from the entire images, the ROI of the optic disc and the ROI of the macula, respectively. We found the model combining all the features has the best classification performance and obtained a sensitivity of 92.5%, a specificity of 92.1% and an accuracy of 92.4%, which is significantly different from other models (p<0.001).
CONCLUSIONS: We used two methods to improve the classification performance and found the best model to detect glaucoma on colour fundus retinal images. It can become a cost-effective and relatively more accurate glaucoma screening tool than conventional methods.

OBJECTIVE: We evaluated longitudinal autoantibody changes after intravenous methylprednisolone (IVMP), compared them with those in untreated patients and identified prognostic factors for treatment response.
METHODS: In this single-centre, retrospective, observational study, a total of 163 individuals diagnosed with moderate-to-severe thyroid eye disease were enrolled and followed for 12 months. Depending on whether IVMP was administered, we divided the patients into treatment and control groups. Based on the effect of IVMP on TSH receptor (TSH Rc) antibody level, we divided the patients into Ab declined and Ab not declined groups.We evaluated the time, group and interaction associations with the longitudinal autoantibody titres over 12 months using generalised estimating equations. Using multivariable logistic regression, we investigated the prognostic factors for a poor response to IVMP.
RESULTS: In the IVMP group, the TSH Rc antibody (Ab) titre decreased rapidly for 6 months and then decreased slowly until 12 months, becoming similar to the control group at 12 months. This suggests a difference in the decreasing pattern over time between the IVMP and control groups (group and time interaction p=0.029). Total cholesterol (OR 1.0217 (95% CI 1.0068 to 1.0370), p=0.0043) was a significant prognostic factor for the steroid response. The threshold total cholesterol value to distinguish between Ab declined and Ab not declined was 186 mg/dL.
CONCLUSIONS: IVMP significantly decreased the TSH Rc Ab level for the 3 months after treatment, compared with the no-treatment group, but the groups did not differ significantly after 12 months. Patients with high total cholesterol levels generally showed a poor response to IVMP.

OBJECTIVE: To explore the sensitive components of full-field electroretinography (ERG) as indicators of retina function at the onset of acute ischaemic central retinal vein occlusion (CRVO).
METHODS: 11 patients (11 eyes) with ischaemic CRVO and 32 patients (32 eyes) with non-ischaemic CRVO who presented with first-episode unilateral CRVO within 1 month of symptom onset and with no previous intervention were examined by the International Society for Clinical Electrophysiology of Vision standard ERG.
RESULTS: A significant amplitude decline and peak time delay in light-adapted (LA) 3 ERG and LA 30 Hz flicker ERG (p<0.05 for all) was found in the ischaemic CRVO eyes, compared with the non-ischaemic CRVO eyes. The b/a amplitude ratio of dark-adapted (DA) 3 ERG, DA 10 ERG and LA 3 ERG was significantly different between the ischaemic and non-ischaemic groups (p<0.05 for all). Regarding oscillatory potentials (OPs), the amplitudes of OP1, OP2 and OP3 as well as the sum of DA 3 OP1-4 amplitudes (∑OPs) showed significant changes (p<0.01 for all) between two groups. No peak time delay of OPs was found between the ischaemic and non-ischaemic CRVO eyes.
CONCLUSIONS: The amplitude of DA 0.01 ERG, components of LA 3 ERG and LA 30 Hz flicker ERG, and the b/a amplitude ratio could be among the most sensitive indicators in patients with acute ischaemic CRVO. The amplitudes of OP1, OP2, OP3 and ∑OPs in the CRVO eyes were reduced to 40% of the control values, showing that this quantitative method is reliable for detecting ischaemic retinal diseases, even in early stage.

OBJECTIVE: Female choroideremia carriers present with a spectrum of disease severity. Unlike in men, the rate of disease progression has not been well characterised in carriers. This longitudinal study aimed to determine the rate of retinal degeneration in choroideremia carriers, using multimodal imaging and microperimetry.
METHODS: Choroideremia carriers previously seen at Oxford Eye Hospital (United Kingdom) between 2012 and 2017 returned for testing between 2015 and 2023, providing up to 11 years\' follow-up data. Participants had optical coherence tomography, fundus-tracked microperimetry and fundus autofluorescence (FAF) imaging performed.
RESULTS: Thirty-four eyes of 17 choroideremia carriers were examined using multimodal imaging. Median age was 44 (range: 15-73) years at baseline and median follow-up duration was 7 (range: 1-11) years. At baseline, phenotype was classified as fine (n=5 eyes), coarse (n=13 eyes), geographic (n=12 eyes) or male pattern (n=4 eyes). Thirteen patients showed no change in phenotype classification, four showed slight changes associated with choroideremia-related retinal degeneration. Despite this, carriers with severe retinal phenotypes had a statistically significant decline in average retinal sensitivity (-0.7 dB and -0.8 dB per year, respectively, p<0.001), area of geographic loss defined by FAF (+2.5 mm2 and +3.7 mm2 per year, respectively, p<0.001) and thinning of the photoreceptor complex (up to -2.8 microns and -10.3 microns per year, p<0.001).
CONCLUSIONS: Choroideremia carriers, particularly those with severe retinal phenotypes, exhibit progressive retinal degeneration, as evident by multimodal imaging biomarkers and functional testing. Clinicians should not rely on retinal severity classification alone to assess disease progression.

OBJECTIVE: To compare the diagnostic utility of metagenomic deep sequencing (MDS) to cytology, flow cytometry and gene rearrangement by PCR in ocular samples of patients with suspected vitreoretinal lymphoma (VRL).
METHODS: Patients with suspected VRL underwent ocular sampling of one or both eyes at the Emory Eye Center from September 2017 to June 2022. Ocular samples were evaluated with MDS and conventional diagnostics. MDS was performed at the Ralph and Sophie Heintz Laboratory at the F.I. Proctor Foundation. Relevant demographic and clinical data were retrospectively collected from medical records. Patients were diagnosed with VRL based on clinical assessment and conventional diagnostic testing.
RESULTS: This study included 13 patients with suspected VRL who underwent diagnostic vitrectomy, including 1 patient who had an additional subretinal biopsy. Six patients (46.2%) were diagnosed with VRL. Among patients diagnosed with VRL, MDS detected pathogenic mutations in 5 out of 6 patients (83.3%) while cytology was positive for VRL in 4 out of 6 patients (66.7%), flow cytometry in 4 out of 4 patients (100.0%) and PCR in 4 out of 4 patients (100.0%). MDS detected mutations in MYD88 in 2 out of 6 patients diagnosed with VRL. In 7 patients (53.8%) not diagnosed with VRL, MDS detected pathogenic lymphoma mutations in 2 patients (28.6%).
CONCLUSIONS: MDS detected pathogenic mutations in five out of six patients diagnosed with VRL, including in two patients with negative cytology, demonstrating its potential to improve diagnostic rates of VRL as an adjunctive test.

OBJECTIVE: Recent decades have seen significant advances in both structural and functional testing of retinal disease. However, the current clinical value of specific testing modalities, as well as future trends, need to be clearly identified in order to highlight areas for further development in routine care and clinical trials.
METHODS: We designed a modified two-round Delphi study to obtain the opinion of a multidisciplinary group of 33 international experts involved in the field of retinal disease management/research to determine the level of agreement and consensus regarding the value and performance of specific structural and functional testing methods for retinal disease. On a Likert scale, a median of 1-2 indicated disagreement with the statement, and 5-6 indicated agreement with the statement. An IQR of ≤2 indicated consensus in the responses. Several questions also allowed comments on responses.
RESULTS: There was overall agreement that structural testing currently predominates for detection and monitoring. There was moderate agreement that functional testing remains important and will continue to do so in the future because it provides complementary information. Certain respondents considered that properly designed and applied psychophysical tests are as reliable and repeatable as structural observations and that functional changes are the most important in the long run. Respondents considered future care and research to require a combination of structural and functional testing with strong consensus that the relative importance will depend on disease type and stage.
CONCLUSIONS: The study obtained important insights from a group of international experts regarding current and future needs in the management of retinal disease using a mix of quantitative and qualitative approaches. Responses provide a rich range of opinions that will be of interest to researchers seeking to design tests for future patient care and clinical trials.

BACKGROUND: Tuberculosis (TB)-immunoreactivity, measured in vivo (tuberculin skin test (TST)) or in vitro (interferon gamma release assay (IGRA)), can be found in latent, active or even following clearance of TB infection. In this case-control study, we compared the systemic and ocular outcomes between patients with or without TB-immunoreactivity, who received immunomodulatory therapy (IMT) for non-infectious uveitis.
METHODS: We retrospectively reviewed charts of patients with (cases) or without (controls) TB-immunoreactivity (TST±IGRA), who received conventional IMT for ≥6 months, for the treatment of non-infectious uveitis. Patients who received prior or concomitant anti-TB therapy were excluded. Systemic and ocular outcomes were compared between both groups.
RESULTS: 36 cases and 70 controls (gender-matched and age-matched) were included. New-onset pulmonary or extrapulmonary TB developed in one case and none of the controls. Based on this outcome, the absolute risk increase for systemic TB reactivation was noted to be 0.028 (95% CI 0.005 to 0.051) and the number needed to harm was 36. The incidence of persistent or recurrent (worsening ≥2 grades) intraocular inflammation during IMT was comparable between both groups (cases 18/36, controls 35/70, p=1.0). A change in anatomical site of presentation at recurrence was not seen in any case, but in six controls (p=0.15). No new focal chorio-retinal lesions were noted in either group.
CONCLUSIONS: Conventional IMT has a very low risk of systemic TB reactivation, and no additional detrimental effect on ocular outcomes, in TB-immunoreactive patients with non-infectious uveitis.

The rapid advancements in generative artificial intelligence are set to significantly influence the medical sector, particularly ophthalmology. Generative adversarial networks and diffusion models enable the creation of synthetic images, aiding the development of deep learning models tailored for specific imaging tasks. Additionally, the advent of multimodal foundational models, capable of generating images, text and videos, presents a broad spectrum of applications within ophthalmology. These range from enhancing diagnostic accuracy to improving patient education and training healthcare professionals. Despite the promising potential, this area of technology is still in its infancy, and there are several challenges to be addressed, including data bias, safety concerns and the practical implementation of these technologies in clinical settings.

BACKGROUND: Unpreserved single-dose unit (SDU) eye drops are commonly used to avoid benzalkonium chloride-related toxicity. Although intended for single use, many patients report off-label repeated use of SDUs over a prolonged period. We investigated whether repeated use of dexamethasone 0.1% SDUs in the same patient increases the bacterial contamination rate.
METHODS: We prospectively enrolled patients scheduled for inpatient corneal and glaucoma surgery receiving dexamethasone 0.1% SDU four times per day from the same vial. To assess contamination rates, one drop from the vial was cultured immediately after opening the SDU (t0), 10 hours later after four drop applications (t10) and 24 hours after opening without further drop applications (t24). Conjunctival swabs were taken before and after drop application. Contamination rate was assessed with a standard clinical culturing protocol without introducing a positive control.
RESULTS: 110 eyes of 109 patients were evaluated. Drops collected immediately after opening the SDU (t0) were contaminated in 9/110 cultures (8.1%). At t10, 13/110 cultures were contaminated (11.8%; p=0.267) and 11/110 at t24 (10.0%; t24 vs t0; p=1.00). In 5 of 21 cases of contaminated drops at t10 and/or t24, the same isolates were cultured from the initial conjunctival swab and the SDU. In three cases, the same bacterial species was found in consecutive samples.
CONCLUSIONS: The contamination rate of the SDU did not increase after multiple use within 24 hours. Contamination from fingertip flora was more likely than from ocular surface flora. Reuse of dexamethasone 0.1% SDU in the same patient within 24 hours appears to be safe.

OBJECTIVE: To evaluate the diagnostic accuracy of spectral-domain optical coherence tomography (SD OCT) combined with OCT angiography (OCTA) for myopic myopic macular neovascularisation (MNV) activity.
METHODS: Both eyes of patients with myopic MNV diagnosed with fluorescein angiography (FA), SD OCT and OCTA were assessed by unmasked investigators. The images were deidentified and randomised before graded by masked investigators, who determined the presence of active myopic MNV by using SD OCT together with OCTA without FA and by FA alone, respectively. The findings of masked investigators were compared with unmasked investigators.
RESULTS: 213 eyes of 110 patients comprising 499 imaging episodes were eligible for grading. For diagnosing new-onset myopic MNV without FA, combined use of SD OCT and OCTA had a sensitivity of 0.94, specificity of 0.84 and area under the curve (AUC) of 0.92. FA had a sensitivity of 0.52 (p<0.01), specificity of 0.80 (p=0.38) and AUC of 0.66 (p<0.01). For recurrent myopic MNV, the combination of SD OCT and OCTA had a sensitivity of 0.98, specificity of 0.78 and AUC of 0.88. FA had a sensitivity of 0.50 (p=0.04), specificity of 0.76 (p=0.85) and AUC of 0.63 (p=0.01). Myopic traction maculopathy was more frequently associated with recurrent myopic MNV (p<0.01).
CONCLUSIONS: SD OCT with dense volumetric scan was highly sensitive for diagnosing myopic MNV. The addition of OCTA improved the diagnostic specificity without FA. Monitoring of the longitudinal changes on SD OCT and judicious use of FA is a reliable surveillance strategy for myopic MNV.