Improved accuracy of spectral-domain optical coherence tomography and optical coherence tomography angiography for monitoring myopic macular neovascularisation activity.

BACKGROUND/AIMS: 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). CONCLUSION: 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.

Genetic association of TIE2 with diabetic retinopathy and diabetic macular edema.

PURPOSE: To evaluate the associations of the TIE2 gene with diabetic retinopathy (DR) and diabetic macular edema (DME). METHODS: This study included a Chinese cohort of 285 non-proliferative DR patients and 433 healthy controls. The DR patients were classified further into those with or without DME. Thirty haplotype-tagging single-nucleotide polymorphisms (SNPs) in TIE2 were genotyped using TaqMan technology. Associations of DR and subtypes were analyzed by logistic regression adjusted for age and sex. Stratification association analysis by sex was performed. RESULTS: TIE2 rs625767 showed a nominal but consistent association with DR [odds ratio (OR) = 0.71, P = 0.005] and subtypes (DR without DME: OR = 0.69, P = 0.016; DME: OR = 0.73, P = 0.045). SNP rs652010 was consistently associated with overall DR (OR = 0.74, P = 0.011) and DR without DME (OR = 0.70, P = 0.016), but not with DME. Moreover, SNPs rs669441, rs10967760, rs549099 and rs639225 showed associations with overall DR, whilst rs17761403, rs664461 and rs1413825 with DR without DME. In stratification analysis, three SNPs, rs625767 (OR = 0.62, P = 0.005), rs669441 (OR = 0.63, P = 0.006) and rs652010 (OR = 0.64, P = 0.007), were associated with DR in females, but not in males. Moreover, one haplotype T-T defined by rs625767 and rs669441 was significantly associated with DR in females only. CONCLUSIONS: This study revealed TIE2 as a susceptibility gene for DR and DME in Chinese, with a sex-specific association in females. Further validation should be warranted.

Displacement of Submacular Hemorrhage Using Subretinal Cocktail Injection versus Pneumatic Displacement: A Real-World Comparative Study.

INTRODUCTION: The objective of this study was to compare the outcome of submacular hemorrhage (SMH) displacement using pneumatic displacement with intravitreal expansile gas versus pars plana vitrectomy (PPV) with subretinal injection of tissue plasminogen activator (tPA), anti-vascular endothelial growth factor (VEGF) agent, and air as primary surgery. METHODS: Retrospective interventional case series of 63 patients who underwent surgical displacement of SMH secondary to neovascular age-related macular degeneration (nAMD) or polypoidal choroidal vasculopathy (PCV) from May 1, 2015, to October 31, 2022. Medical records were reviewed for diagnosis, logMAR visual acuity (VA), central subfield thickness (CST), and postoperative displacement rates and complications up to 12 months after operation. RESULTS: The diagnosis was nAMD in 24 (38.1%) and PCV in 39 (61.9%) eyes. There were 40 (63.5%) eyes in the pneumatic displacement group (38 received C3F8, 2 received SF6) and 23 (36.5%) eyes in the subretinal cocktail injection. Mean baseline VA was 1.46 and 1.62, respectively (p = 0.404). The subretinal injection group had more extensive SMH (p = 0.005), thicker CST (1,006.6 µm vs. 780.2 µm, p = 0.012), and longer interval between symptom and operation (10.65 vs. 5.53 days, p < 0.001). The mean postoperative VA at 6 months was 0.67 and 0.91 (p = 0.180) for pneumatic displacement and subretinal injection groups, respectively, though VA was significantly better in the pneumatic group at 12-month visit (0.64 vs. 1.03, p = 0.040). At least 10 mean change in VA were >10 letters gain in both groups up to 12 months. Postoperative CST reduction was greater (625.1 µm vs. 326.5 µm, p = 0.008) and complete foveal displacement (87.0% vs. 37.5%), p < 0.001, odds ratio [OR] = 11.1) and displacement to arcade or beyond (52.5% vs. 17.5%, p = 0.009, OR = 5.15) were more frequent in the subretinal injection group. Two patients with failed pneumatic displacement were successfully treated with subretinal cocktail injection as a second operation. CONCLUSION: Surgical displacement of SMH leads to clinically meaningful improvement in VA. PPV with subretinal cocktail injection is more effective than pneumatic displacement in displacing SMH with similar safety profile despite longer interval before operation, higher CST, and more extensive SMH at baseline. Retinal surgeons could consider this novel technique in cases with thick and extensive SMH or as a rescue secondary operation in selected cases.

IMPACT OF GAS/AIR TAMPONADE ON REFRACTIVE OUTCOMES AFTER FLANGED INTRASCLERAL INTRAOCULAR LENS FIXATION.

PURPOSE: This study aims to investigate the postoperative refractive outcomes in eyes that underwent the flanged intrascleral intraocular lens (IOL) fixation combined with vitrectomy with or without gas/air tamponade. METHODS: The eyes were divided into two groups (Group A; eyes that underwent flanged intrascleral IOL fixation with gas/air tamponade, and Group B; eyes that underwent flanged intrascleral IOL fixation without gas/air tamponade). The predicted spherical equivalent (SE) refraction values were calculated using the Sander-Retzlaff-Kraff Theoretical formula. Then, the prediction error was calculated by subtracting the predicted SE refraction from the postoperative objective SE refraction and the absolute prediction error was calculated as the absolute value of the prediction error for each eye. RESULTS: A total of 68 eyes were included in the current study. There was a significant correlation between the predicted and postoperative SE refraction in both groups (Group A, r = 0.968, P < 0.0001, Group B, r = 0.943, P < 0.0001, linear regression analysis). The prediction error demonstrated a mild myopic shift after the flanged intrascleral IOL fixation in both groups (Group A, -0.40 ± 0.96 diopter, Group B, -0.59 ± 0.95 diopter). There was no significant difference in prediction error and absolute prediction error between the two groups ( P = 0.44, P = 0.70, Wilcoxon rank sum test). CONCLUSION: The postoperative SE refraction after flanged intrascleral IOL fixation was not influenced by gas/air tamponade.

Hyperreflective material in patients with non-neovascular pachychoroid disease.

BACKGROUND: This study aimed to report eleven cases of non-neovascular pachychoroid disease with hyperreflective material (HRM) that occurred in Japanese patients. METHODS: A retrospective review of data from eleven patients who had non-neovascular retinal pigment epithelium (RPE) protrusion with HRM in the neurosensory retina between March 2017 and June 2022 was conducted. Clinical examination, color fundus photography, fluorescein angiography, spectral-domain optical coherence tomography (SD-OCT), and OCT angiography data were analyzed. Main outcome measures were patient characteristics, changes in SD-OCT findings, and symptom outcomes. RESULTS: All cases had RPE protrusion and HRM with dilated choroidal veins, which were characteristic of pachychoroid disease. However, none of the cases had macular neovascularization (MNV). In 9 eyes (81.8%), HRM improved spontaneously without intervention and resulted in alterations in RPE, referred to as pachychoroid pigment epitheliopathy (PPE) or focal choroidal excavation (FCE). In these cases, symptoms such as metamorphopsia and distortion improved without treatment. In the remaining two cases (18.2%), HRM still persisted during the follow-up period. CONCLUSION: There are some cases of non-neovascular pachychoroid disorder with HRM, which might be a new entity of pachychoroid spectrum disease or an early stage of PPE or FCE. These cases should not be misdiagnosed as MNV, and careful observation is necessary.

Review on the Safety and Efficacy of Brolucizumab for Neovascular Age-Related Macular Degeneration From Major Studies and Real-World Data.

Frequent antivascular endothelial growth factor injections in neovascular age-related macular degeneration (nAMD) often lead to poor compliance and suboptimal outcomes. A longer-acting agent has been a pressing unmet need until recently. Brolucizumab, an antivascular endothelial growth factor agent, is a single-chain antibody fragment approved by the US Food and Drug Administration (FDA) on October 8, 2019, for treating nAMD. It delivers more molecules at equivalent volumes of aflibercept, thus achieving a longer-lasting effect. We reviewed literature published in English between January 2016 and October 2022 from MEDLINE, PubMed, Cochrane database, Embase, and Google scholar using the keywords: "Brolucizumab, real-world data, intraocular inflammation (IOI), safety, and efficacy". Brolucizumab showed reduced injection frequency, better anatomic outcomes, and noninferior vision gains compared with aflibercept in HAWK and HARRIER studies. However, post hoc studies on brolucizumab revealed a higher-than-expected incidence of IOI, leading to the early termination of 3 studies: MERLIN, RAPTOR, and RAVEN for nAMD, branch retinal vein occlusion, and central retinal vein occlusion, respectively. Contrastingly real-world data showed encouraging outcomes in terms of fewer IOI cases. The subsequent amendment of the treatment protocol resulted in reduced IOI. Thereafter US FDA approved its use in diabetic macular edema on June 1, 2022. Based on major studies and real-world data, this review shows that brolucizumab is effective for treating naive and refractory nAMD. The risk of IOI is acceptable and manageable, but proper preinjection screening and high-vigilance care of IOI are needed. More studies are warranted to evaluate further the incidence, best prevention, and treatment measures for IOI.

Performance, safety and efficiency comparison between 10,000 and 5000 cuts per minute vitrectomy using a 25G cutter: a prospective randomized controlled study.

PURPOSE: This study aims to compare the performance of the 25+® UltraVit® 5000 cuts per minute (cpm) vitrectomy probe versus the 25+ ® Ultravit 10,000 cpm® beveled tip, dual drive vitrectomy probe. METHOD: In this prospective randomised controlled clinical trial, 52 eyes of 52 consecutive patients were randomized into either the 10,000 cpm (25 patients) or 5000 cpm vitrectomy group (27 patients). Patients were evaluated preoperatively, intraoperatively, and postoperatively on the first day, and at 1 week, 1 month and 3 months. The main outcome measures were vitrectomy time, and secondary endpoints were time to induction of posterior vitreous detachment, intraoperative complications, and number of instruments used. RESULTS: The vitrectomy time was shorter in the 10,000 cpm group (413.7 s) compared to the 5000 cpm group (463.4 s), although there was no significant difference (p = 0.5999). One patient had an iatrogenic retinal break in the 10,000 cpm group while two patients had an iatrogenic retinal break in the 5000 cpm group. The time for posterior vitreous detachment (PVD) induction and the number of instruments used were not significantly different between the two groups. CONCLUSION: The difference in vitrectomy times between the 10,000 cpm vitrectomy probe and the 5000 cpm cutter were not statistically significant. This may suggest that other factors affect efficiency rather than the limitations of equipment.

Recent Advances in Clinical Applications of Imaging in Retinal Diseases.

Many diseases that cause visual impairment, as well as systemic conditions, manifest in the posterior segment of the eye. With the advent of high-speed, high-resolution, reliable, and noninvasive imaging techniques, ophthalmologists are becoming more dependent on ocular imaging for disease diagnosis, classification, and management in clinical practice. There are rapid advances on the indications of multimodal retinal imaging techniques, including the application of ultra-widefield fundus angiography, fundus autofluorescence, optical coherence tomography, as well as optical coherence tomography angiography. This review summarizes and highlights the clinical applications, latest indications, and interpretations of multimodal imaging in age-related macular degeneration, polypoidal choroidal vasculopathy, diabetic macular edema, central serous chorioretinopathy, diabetic retinopathy, retinal vein occlusion, and uveitis.

OCT-based biomarkers for predicting treatment response in eyes with centre-involved diabetic macular oedema treated with anti-VEGF injections: a real-life retina clinic-based study.

BACKGROUND/AIMS: To determine whether a combination of baseline and change in spectral domain-optical coherence tomography (SD-OCT)-based biomarkers can predict visual outcomes in eyes with diabetic macular oedema (DMO) treated with antivascular endothelial growth factors (VEGF) injections. METHODS: This is a retrospective cohort study conducted in Hong Kong, China. 196 eyes with centre-involving DMO, who received anti-VEGF injections between 1 January 2011 and 30 June 2018 were recruited. Medical records of the participants were retrieved retrospectively, visual acuity (VA) at baseline, 6, 12 and 24 months and SD-OCT before initiation and after completion of anti-VEGF treatment were obtained. The SD-OCT images were evaluated for the morphology of DMO, vitreomacular status, presence of disorganisation of retinal inner layers (DRIL), sizes of intraretinal cysts, visibility of external limiting membrane (ELM), ellipsoid zone (EZ) and cone outer segment tip (COST) and the presence of hyper-reflective foci in retina or the choroid. RESULTS: The presence of baseline DRIL, hyper-reflective foci in retina and disruption of ELM/EZ and COST were associated with worse baseline and subsequent VA up to 24 months after treatment. Improvement in DRIL (p=0.048), ELM/EZ (p=0.001) and COST (p=0.002) disruption after treatment was associated with greater improvement in VA at 12 months. Eyes with cystoid macular oedema (p=0.003, OR=8.18) and serous retinal detachment (p=0.011, OR=4.84) morphology were more likely to achieve at least 20% reduction in central subfield thickness. CONCLUSION AND RELEVANCE: Baseline SD-OCT biomarkers and their subsequent change predict VA and improvement in vision in eyes with DMO treated with anti-VEGF injections. We proposed an SD-OCT-based system that can be readily used in real-life eye clinics to improve decision making in the management of DMO.

Massive retinal infiltrates as the presenting sign of chronic myeloid leukemia: Clinical and imaging features of leukemic retinopathy.

PURPOSE: To describe the clinical and optical coherence tomography (OCT) features of two cases with bilateral diffuse retinal infiltrates as the only presenting feature of chronic myeloid leukemia (CML) on initial diagnosis and upon relapse. METHODS: We reported two patients with CML, one at initial diagnosis and one in remission who presented with bilateral subacute visual impairment. Fundal examination revealed bilateral symmetrical leukostatic appearance with increased vascular tortuosity, diffuse retinal infiltrates with size up to 6 disk diameters, retinal hemorrhages, and Roth's spots. OCT showed multiple intra-retinal hyper-reflective foci corresponding to intra-retinal hemorrhages, and outer retinal hyper-reflective foci in area corresponding to retinal infiltrate. The different retinal layers were relatively preserved and distinguishable. RESULTS: White cell count (WCC) were elevated in both patients ranging from 544 to 810 × 109/L. Bone marrow biopsy confirmed the diagnosis of CML in the patient without prior diagnosis and relapse of CML in another patient. Cytogenetic test detected Abelson murine leukemia (ABL) - breakpoint cluster region (BCR) fusion transcript in both cases. Both patients were started on oral imatinib, subsequently WCC returned to within normal values in both cases. Vision and OCT abnormalities improved and reduction in retinal hemorrhages and infiltrates were observed in follow up. CONCLUSION: This report highlights the important role of ophthalmologists and detailed fundus examination in making a prompt diagnosis of leukemia in patients with visual complaints. Appropriate systemic investigation and hematologist referrals for prompt treatment of CML may improve survival rate and preserve vision.