Characteristics of ocular hypertension and uveitic glaucoma among patients with noninfectious uveitis.

OBJECTIVE: Ocular hypertension and uveitic glaucoma are important downstream sequela of noninfectious uveitis (NIU). Herein, we describe the clinical outcomes of NIU cases with ocular hypertension and uveitic glaucoma. DESIGN: Retrospective cohort study. PARTICIPANTS: All adults (≥18 years) with NIU under the care of uveitis subspecialty tertiary care clinics between 2010 and 2021 were included. METHODS: The primary outcomes were baseline and final visual acuity. RESULTS: A total of 216 patients out of 914 (23.6%) cases with NIU had ocular hypertension or uveitic glaucoma over the study period. Of all patients with ocular hypertension or uveitic glaucoma, 46% were corticosteroid responders. Baseline and last median visual acuities were better for the ocular hypertension patients compared with patients with uveitic glaucoma (p < 0.001). A higher proportion of patients with uveitic glaucoma than patients with ocular hypertension required glaucoma surgery (p < 0.001). The regression analyses suggested that baseline visual acuity and anatomical classification are significant predictors of last visual acuity, whereas diagnosis of ocular hypertension versus uveitic glaucoma were significant predictors of requirement for glaucoma surgery (p < 0.001). CONCLUSION: A quarter of patients with NIU in this study developed ocular hypertension or uveitic glaucoma. Approximately half of the patients with ocular hypertension or uveitic glaucoma were deemed to be corticosteroid responders. Baseline and last visual acuity outcomes are better amongst ocular hypertension patients compared with those with uveitic glaucoma. Poor baseline visual acuity and panuveitis are predictors of worse vision at last follow-up. Additionally, diagnosis of uveitic glaucoma was a significant predictor of requirement for glaucoma surgery.

RETINAL OPTICAL COHERENCE TOMOGRAPHY IMAGING BIOMARKERS: A Review of the Literature.

PURPOSE: The aim of this literature review was to summarize novel optical coherence tomography (OCT) imaging biomarkers that have recently been described in the literature and are frequently encountered clinically. METHODS: The literature was reviewed to identify novel OCT biomarkers reported to date. A descriptive summary of all terms and representative illustrations were provided to highlight the most relevant features. RESULTS: Thirty-seven OCT terminologies were identified. The vitreomacular interface disorder group included the four stages of epiretinal membrane, macular pseudohole, tractional lamellar hole (LH), degenerative LH, cotton ball sign, and foveal crack sign. The age-related macular degeneration group included outer retinal tubulation, multilayered pigment epithelial detachment, prechoroidal cleft, onion sign, double-layer sign, complete outer retinal atrophy, complete retinal pigment epithelium and outer retinal atrophy, and reticular pseudodrusen. The uveitic disorder group consisted of bacillary layer detachment, syphilis placoid, rain-cloud sign, and pitchfork sign. The disorders relating to the toxicity group included flying saucer sign and mitogen-activated protein kinase (MEK) inhibitor-associated retinopathy. The disorders associated with the systemic condition group included choroidal nodules and needle sign. The pachychoroid spectrum group included pachychoroid and brush border pattern. The vascular disorder group included pearl necklace sign, diffuse retinal thickening, disorganization of retinal inner layers, inner nuclear layer microcysts, hyperreflective retinal spots, paracentral acute middle maculopathy, and acute macular neuroretinopathy. The miscellaneous group included omega sign (ω), macular telangiectasia (type 2), and omega sign (Ω). CONCLUSIONS: Thirty-seven OCT terminologies were summarized, and detailed illustrations consolidating the features of each biomarker were included. A nuanced understanding of OCT biomarkers and their clinical significance is essential because of their predictive and prognostic value.

Evaluating the long-term biological stability of cytokine biomarkers in ocular fluid samples.

PURPOSE: The quality of biological fluid samples is vital for optimal preanalytical procedures and a requirement for effective translational biomarker research. This study aims to determine the effects of storage duration and freeze-thawing on the levels of various cytokines in the human aqueous humour and vitreous samples. METHODS AND ANALYSIS: Human ocular aqueous humour and vitreous samples were obtained from 25 eyes and stored at -80°C for analysis. All samples were assayed for 27 cytokine biomarker concentrations (pg/mL) using a multiplex assay. Four sample storage durations following sample collection were evaluated (1 week, 3 months, 9 months and 15 months). Additionally, samples underwent up to three freeze-thaw cycles within the study period. RESULTS: Among the 27 cytokine biomarkers, concentrations of four cytokines (Interleukin (IL)-2, IL-10, IL-12 and platelet-derived growth factor-BB) were significantly decreased by storage duration at all time points, as early as 3 months following sample collection (range of 9%-37% decline between 1 week and 15 months, p<0.001). Freeze-thawing of up to three cycles did not significantly impact the cytokine biomarker concentrations in aqueous humour or vitreous. Separability of patient-specific cytokine biomarker profiles in the principal component analysis remained relatively the same over the 15 months of storage duration. CONCLUSION: The findings from this study suggest that several intraocular cytokine biomarkers in human aqueous humour and vitreous samples may be susceptible to degradation with long-term storage, as early as 3 months after collection. The overall patient-specific cytokine biomarker profiles are more stable than concentrations of individual cytokines. Future studies should focus on developing guidelines for optimal and standardised sample handling methods to ensure correct research findings about intraocular biomarkers are translated into clinical practice.

Clinical characteristics of non-infectious uveitis treated with and without systemic immunomodulatory therapy.

OBJECTIVE: To compare the patient characteristics and long-term outcomes for those treated with and without systemic immunomodulatory therapy (IMT) for non-infectious uveitis (NIU). DESIGN: Retrospective cohort study. PARTICIPANTS: All consecutive adults with NIU receiving care at 5 uveitis subspecialty tertiary care clinics between 2010 and 2021. METHODS: Clinical outcomes were evaluated on initial presentation and at the last available follow-up. The main outcome measures were baseline characteristics and final visual acuity. RESULTS: A total of 914 NIU patients (418 IMT, 496 non-IMT) with a median age of 51.0 years and 57.4% female were identified. Over half the patients had bilateral disease, with a significantly higher proportion of bilateral cases in the IMT group compared with the non-IMT group (p < 0.001). The IMT group was more likely to have chronic uveitis (p < 0.001), with a higher proportion of patients experiencing cataracts and cystoid macular edema (p < 0.001 for both). A significantly higher proportion of non-IMT patients had anterior uveitis and an idiopathic etiology (p < 0.001). Overall, visual acuity improved significantly from baseline to last follow-up in the entire cohort (p < 0.001), with a slightly better improvement in the IMT group. Multivariable linear regression analysis suggested that baseline visual acuity and panuveitis were significant predictors of final visual acuity (p < 0.001 for both). CONCLUSIONS: NIU patients on IMT are often younger, suffer from bilateral and chronic uveitis, and are more likely to have ocular complications. Those in the non-IMT group are more likely to have anterior idiopathic NIU. Baseline visual acuity and panuveitis are the main predictors of final vision outcomes among patients with NIU.

Anatomical and functional outcomes of short-term DensironXTRA heavy silicone oil for rhegmatogenous retinal detachments: a comparative case series.

To assess the safety and efficacy of short-term DensironXTRA tamponade for repair of complicated rhegmatogenous retinal detachments (RRD). This is a retrospective consecutive case series of patients undergoing pars plana vitrectomy (PPV) with intravitreal DensironXTRA and a comparator group with gas (sulfur hexafluoride (SF6) or perfluoropropane (C3F8)) tamponades by a single surgeon between January 2017 and November 2020 at a tertiary care centre. A total of 121 eyes with DensironXTRA and 81 comparator eyes with a gas tamponade were included. The DensironXTRA group had a significantly higher number of cases with inferior breaks (82% vs. 48%; p < 0.0001) and a history of previous PPV for RRD (64% vs. 12%; p < 0.0001). DensironXTRA was removed after a median period of 70 (IQR: 48.5-105.5) days. There was similar anatomical success in both the comparator gas tamponade and DensironXTRA groups (98.8% vs. 97.5%, p = 0.6506). Although both groups experienced a significant improvement in visual acuity, this change was significantly higher in the comparator gas tamponade group versus DensironXTRA group (p = 0.0017). There was no significant change in IOP in the DensironXTRA group (mean difference - 0.7; 95% CI - 1.753 to 0.331, p = 0.1785). The rates of complications were low and not significantly different between the two groups. There was no evidence for central macular thinning with DensironXTRA compared to the contralateral eye without RRD as well as with DensironXTRA in situ versus after its removal. DensironXTRA is a promising short-term tamponade agent with good anatomical and functional outcomes and low rates of complications for the repair of complicated RRDs.

Prophylactic intraocular pressure lowering measures in anti-vascular endothelial growth factor therapy: A systematic review and meta-analysis.

Acute intraocular pressure (IOP) elevation following repeat intravitreal anti-vascular endothelial growth factor (VEGF) injections (IVI) may pose a risk to the integrity of the retinal nerve fiber (RNFL). This meta-analysis investigates the role of IOP-lowering interventions such as an anterior chamber paracentesis (ACP) and IOP-lowering medications on the IOP in patients undergoing IVIs. MEDLINE, EMBASE, and the Cochrane Library were searched up to February, 2021. Studies investigating IOP-lowering interventions in patients undergoing IVI versus controls were included. The primary outcome was the IOP in the short- and long-term post-IVI. Secondary outcomes were changes in the RNFL thickness and best corrected visual acuity (BCVA). ACP at time of anti-VEGF injection significantly lowered IOP immediately post anti-VEGF (WMD: -27.98 mm Hg, P < 0.001). Patients in the ACP group also had significantly thicker RNFL compared to control (WMD: 2.07 um, P < 0.00001) at median follow-up of 16.5 months. IOP-lowering medications (on the day of injection or in the long-term) significantly reduced IOP up to 30 minutes after injection (WMD: -3.31 mm Hg, P = 0.003). This effect was statistically significant between the 2 arms up to 1 month follow-up. There was no difference in BCVA in intervention versus controls. ACP reduces immediate IOP spikes post-IVI and preserves the RNFL in the short- and longterms IOP-lowering medications also reduce IOP spike, with limited data on RNFL thickness.

Prognostic Features of Preoperative OCT in Retinal Detachments: A Systematic Review and Meta-analysis.

TOPIC: To evaluate the prognostic association between preoperative features seen on OCT imaging and postoperative visual acuity (VA) outcomes in rhegmatogenous retinal detachments (RRDs). CLINICAL RELEVANCE: Currently, there is limited literature on the prognostic value of preoperative RRD OCT features. METHODS: A literature search was conducted on Ovid MEDLINE, Ovid Embase, and Cochrane CENTRAL from inception to September 15, 2022. A meta-analysis was performed using a random-effects model. Quality of studies and evidence were assessed using the Joanna Briggs Institute tools and the Grading of Recommendations, Assessment, Development and Evaluation framework, respectively. RESULTS: A total of 1671 eyes of 1670 patients from 29 observational studies were included. Of these, 89% of eyes had a macula-off RRD at presentation. The mean average duration of detachment was 15 ± 10 days. Most eyes (62%) underwent pars plana vitrectomy. Six preoperative OCT features were analyzed: height of retinal detachment (HRD) at the fovea, central macular thickness (CMT), disruption of the ellipsoid zone (EZ) and/or external limiting membrane (ELM), intraretinal cystic cavities (ICCs), outer retinal corrugations (ORCs), and macular detachment. A greater HRD was weakly associated with postoperative VA (Pearson correlation r = 0.35; 95% confidence interval [CI], 0.20-0.48; P < 0.01), and there was no change in this association throughout the postoperative follow-up period. The CMT was not associated with postoperative VA. Eyes with disruption of the EZ and/or ELM had a postoperative VA worse by 0.35 logarithm of the minimum angle of resolution (logMAR) (95% CI, 0.15-0.54; P < 0.01) or 3 Snellen lines. Eyes with ICCs had a postoperative VA worse by 0.14 logMAR (95% CI, 0.01-0.26; P < 0.01) or 2 Snellen lines. Eyes with ORCs did not have a significantly different postoperative VA than eyes without ORCs. Eyes with macular detachment had a postoperative VA worse by 0.15 logMAR (95% CI, -0.31 to 0.00; P = 0.02) or 2 Snellen lines. Overall, the quality of studies ranged from moderate to good (73%-100%). All associations had a low quality of evidence, with CMT being of very low quality. CONCLUSION: Despite the low quality of evidence, a greater HRD, disruption of the EZ and/or ELM, presence of ICCs, and macular detachment were associated with a poor postoperative VA. We propose a standardized nomenclature for consistency and accuracy in reporting preoperative RRD OCT features for future studies. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

PREOPERATIVE GAS FOR PARS PLANA VITRECTOMY: A SURGICAL TECHNIQUE FOR REPAIR OF RHEGMATOGENOUS RETINAL DETACHMENTS WITH MULTIPLE, LARGE, OR INFERIOR BREAKS.

PURPOSE: To describe the role of preoperative gas for pars plana vitrectomy (PGP) as an adjunct to surgical repair of rhegmatogenous retinal detachment (RRD). METHODS: This is a retrospective consecutive case series of all rhegmatogenous retinal detachments with multiple breaks in more than one quadrant, large breaks extending greater than one clock hour, and/or inferior breaks requiring PPV, who received intravitreal injection of sulfur hexafluoride (SF 6 ) or perfluoropropane (C 3 F 8 ) 1-2 weeks before PPV between 2016 and 2020 at a tertiary care center. RESULTS: A total of 109 eyes underwent the PGP technique, 73% of which had macular involvement. The rhegmatogenous retinal detachments on average involved 5.5 (SD 2.1) clock hours with inferior retinal breaks in 51%. Based on clinical examination, subretinal fluid was noted to be dissipated in parts of the detached retina before PPV in 57% of cases. The use of perfluorocarbon heavy liquid or posterior drainage retinotomy was required in 16% of cases. A 95% primary anatomical success rate was achieved over the median 177 (interquartile range 105-526) follow-up days. A final visual acuity of 20/50 or better was achieved in 65%. CONCLUSION: PGP as an adjunct to PPV may facilitate ease of surgery, as well as anatomical and functional success for rhegmatogenous retinal detachments with multiple, large, and/or inferior breaks.

Applications of the Guarded-Needle External Drainage Technique in Vitreoretinal Surgery.

PURPOSE: To describe the surgical technique using the guarded-needle external drainage for a wide variety of applications in vitreoretinal surgery. METHODS: A step-by-step procedure and a surgical video using the guarded-needle external drainage technique are presented. In addition, a series of representative cases with wide-ranging diagnoses who underwent the technique is reviewed. DESCRIPTION AND TECHNIQUE: The guarded-needle using a 27-gauge thin-walled TSK needle (TSK Laboratory International) and a trimmed 70 buckle sleeve are connected to the active extrusion tubing of the vitrectomy machine. External drainage is performed by actively aspirating subretinal fluid using low active vacuum. The guarded-needle external drainage technique is used in cases with bullous detachments, and small and anterior breaks, when performing scleral buckle, for prevention of underfill when using oil tamponade in cases with choroidal effusion, addressing subretinal gas/air, lysing a subretinal band, draining a suprachoroidal hemorrhage, for diabetic tractional retinal detachments, detachments with no definitive break, and subretinal biopsy in exudative detachments. CONCLUSION: The guarded-needle external drainage has a wide range of applications in vitreoretinal surgery.

Prevalence and predictors for being unscreened for diabetic retinopathy: a population-based study over a decade.

OBJECTIVE: To determine the population-level predictors for being unscreened for diabetic retinopathy (DR) among individuals with diabetes in a developed country. DESIGN: A retrospective population-based repeated-cross-sectional study. PARTICIPANTS: All individuals with diabetes (types 1 and 2) aged ≥20 years in the universal health care system in Ontario were identified in the 2011-2013 and 2017-2019 time periods. METHODS: The Mantel-Haenszel test was used for the relative risk (RR) comparison of subcategories stratified by the 2 cross-sectional time periods. RESULTS: A total of 1 145 645 and 1 346 578 individuals with diabetes were identified in 2011-2013 and 2017-2019, respectively. The proportion of patients unscreened for DR declined very slightly from 35% (n = 405 967) in 2011-2013 to 34% (n = 455 027) in 2017-2019 of the population with diabetes (RR = 0.967; 95% CI, 0.964-0.9693; p < 0.0001). Young adults aged 20-39 years of age had the highest proportion of unscreened patients (62% and 58% in 2011-2013 and 2017-2019, respectively). Additionally, those who had a lower income quintile (RR = 1.039; 95% CI, 1.036-1.044; p < 0.0001), were recent immigrants (RR = 1.286; 95% CI, 1.280-1.293; p < 0.0001), lived in urban areas (RR = 1.149; 95% CI, 1.145-1.154; p < 0.0001), had a mental health history (RR = 1.117; 95% CI, 1.112-1.122; p < 0.0001), or lacked a connection to a primary care provider (RR = 1.656; 95% CI, 1.644-1.668; p < 0.0001) had a higher risk of being unscreened. CONCLUSIONS: This population-based study suggests that over 1 decade, 33% of individuals with diabetes are unscreened for DR, and young age, low income, immigration, residing in a large city, mental health illness, and no primary care access are the main predictors.

MACULAR HOLE HYDRODISSECTION TECHNIQUE WITH HUMAN AMNIOTIC MEMBRANE FOR REPAIR OF LARGE MACULAR HOLES.

PURPOSE: To describe a combined surgical technique using the macular hole hydrodissection (MHH) with human amniotic membrane for repair of large macular holes. METHODS: A step-by-step procedure and a surgical video using the combined MHH and human amniotic membrane technique are presented. DESCRIPTION AND TECHNIQUE: As the first step, the MHH separates the adhesions of the macular hole to the underlying retinal pigment epithelium with a soft-tipped cannula through proportional reflux followed by gentle passive aspiration. The human amniotic membrane graft is marked to identify the nonsticky epithelial side and ensure that the stromal layer (sticky and nonshinny) is facing downward toward the retinal pigment epithelium. The graft is then tucked into the space created with MHH between the macular hole edges and the retinal pigment epithelium with closed forceps to decrease the likelihood of the graft from dislocating postoperatively. CONCLUSION: The MHH in combination with the human amniotic membrane is a practical and effective technique for addressing challenging large macular holes.

Retinal nerve fiber layer in frontotemporal lobar degeneration and amyotrophic lateral sclerosis.

Purpose: Tauopathy and transactive response DNA binding protein 43 (TDP-43) proteinopathy are associated with neurodegenerative diseases. These proteinopathies are difficult to detect in vivo. This study examined if spectral-domain optical coherence tomography (SD-OCT) can differentiate in vivo the difference in peripapillary retinal nerve fibre layer (pRNFL) thickness and macular retinal thickness between participants with presumed tauopathy (progressive supranuclear palsy) and those with presumed TDP-43 proteinopathy (amyotrophic lateral sclerosis and semantic variant primary progressive aphasia). Study design: Prospective, multi-centre, observational study. Materials and methods: pRNFL and macular SD-OCT images were acquired in both eyes of each participant using Heidelberg Spectralis SD-OCT. Global and pRNFL thickness in 6 sectors were analyzed, as well as macular thickness in a central 1 mm diameter zone and 4 surrounding sectors. Linear mixed model methods adjusting for baseline differences between groups were used to compare the two groups with respect to pRNFL and macular thickness. Results: A significant difference was found in mean pRNFL thickness between groups, with the TDP-43 group (n = 28 eyes) having a significantly thinner pRNFL in the temporal sector than the tauopathy group (n = 9 eyes; mean difference = 15.46 µm, SE = 6.98, p = 0.046), which was not significant after adjusting for multiple comparisons. No other significant differences were found between groups for pRNFL or macular thickness. Conclusion: The finding that the temporal pRNFL in the TDP-43 group was on average 15.46 µm thinner could potentially have clinical significance. Future work with larger sample sizes, longitudinal studies, and at the level of retinal sublayers will help to determine the utility of SD-OCT to differentiate between these two proteinopathies.

Human Amniotic Membrane Plug for Chronic or Persistent Macular Holes.

PURPOSE: To report on the use of human amniotic membrane for macular holes at 2 Canadian tertiary care centers. DESIGN: Retrospective cohort study. SUBJECTS: Twenty-two patients with persistent or chronic macular holes. METHODS: Macular hole surgery was performed by 3 vitreoretinal surgeons. MAIN OUTCOME MEASURES: Macular hole closure with complete plugging by human amniotic membrane on spectral-domain OCT. RESULTS: The closure rate was 91% (20 of 22; median follow-up, 7 months), with no statistically significant visual acuity change overall. Complications included subretinal silicone oil (5%), choroidal neovascularization (5%), atrophy (5%), and cystoid macular edema (9%). CONCLUSIONS: Anatomical success with limited visual recovery was observed.

DENSIRON 68 HEAVY SILICONE OIL AS A SHORT-TERM INTRAOCULAR TAMPONADE FOR MACULA-ON INFERIOR RETINAL DETACHMENTS-A CASE SERIES.

PURPOSE: To describe our experience using short-term heavy silicone oil (Densiron 68) for macula-on inferior rhegmatogenous retinal detachments with inferior retinal breaks. METHODS: Retrospective, consecutive, observational case series. Data were retrospectively collected from the medical records of patients who underwent pars plana vitrectomy and Densiron 68 endotamponade for macula-on rhegmatogenous retinal detachment repair. RESULTS: Eight patients were included in the study. The mean patient age was 57.1 ± 12.3 (±SD) years. The mean time to Densiron 68 removal was 57.8 ± 17.8 (±SD) days (ranging from 24 to 83 days). One patient (12.5%) detached three weeks after Densiron 68 removal and required further surgery. All patients were attached at last follow-up with a mean follow-up of 192 days. The mean final best-corrected visual acuity was 20 of 40 (0.29 logarithm of the minimum angle of resolution) similar to the 20 of 45 preoperative best-corrected visual acuity (0.35 logarithm of the minimum angle of resolution, P = 0.501). No significant emulsification was noted before or during the removal of the Densiron 68. Two patients developed an increase in intraocular pressure before Densiron 68 removal that resolved after removal. One patient developed cystoid macular edema that resolved with a short course of topical medications, and one patient had persistent CME that required an intravitreal triamcinolone acetate 1% injection. CONCLUSION: The high anatomic success rate, good visual outcomes, and minimal complications suggest that Densiron 68 can be considered as a short-term tamponade for macula-on retinal detachments with inferior pathology.

A prospective randomized clinical trial comparing nepafenac, intravitreal triamcinolone and no adjuvant therapy for epiretinal membrane.

PURPOSE: To compare the efficacy of topical nepafenac 0.1% versus intravitreal triamcinolone acetonide (IVTA) at the conclusion of vitrectomy surgery versus no adjuvant therapy (NAT) in improving macular morphology post-operatively in patients undergoing vitrectomy for epiretinal membrane (ERM), as measured by optical coherence tomography (OCT) imaging and best-corrected visual acuity (BCVA). METHODS: Design: Prospective randomized clinical trial Setting: Multi-centre 80 patients scheduled to undergo vitrectomy surgery for idiopathic ERM were randomized to receive either IVTA (4 mg/0.1 cc) at the end of surgery, topical nepafenac sodium 0.1% TID for 1 month post-operation or no adjuvant treatment (NAT). Optical coherence tomography (OCT) imaging, best-corrected visual acuity and intraocular pressure (IOP) were measured before surgery, and 1 and 2 months post-operation. RESULTS: Although all three groups showed reduction in macular thickness post-operation, the NAT group showed the most improvement, with a reduction of 136.18 ± 29.84 µm at two months. There was no statistically significant difference in macular thickness between the groups at each time point, p = 0.158. The NAT group also had the best recovery in BCVA with an improvement of 0.207 logMAR (10.35 letters) at two months post-operation. There was no statistically significant difference in BCVA between the groups, p = 0.606. There was statistically significant difference in the IOP between the three groups, p = 0.04 only at 1-month visit. The IVTA group had the highest rise in average IOP at both 1 and 2 months post-operation (2.72 and 1.58 mmHg, respectively). CONCLUSION: Our study data suggest there was no advantage in the use of topical nepafenac or IVTA for post-vitrectomy ERM surgery.