The use of microinvasive invasive glaucoma surgery (MIGS) in the treatment of glaucoma has increased exponentially over the last 10 years. However, practice patterns vary widely given the relative newness of these technologies. Some surgeons perform two or more MIGS simultaneously, such as those that target aqueous production and those that target aqueous outflow. These combined MIGS (cMIGS) may result in lower intraocular pressure (IOP) and reduced medication burden as compared to single MIGS (sMIGS). Current evidence suggests some cMIGS are more effective in reducing medication burden for at least 12 months versus sMIGS. This review focuses on the current evidence related to the efficacy of cMIGS as well as novel combinations of standalone MIGS, limitations of the current literature, and future directions for research.
BACKGROUND: Ultra-thin Descemet stripping automated endothelial keratoplasty (UT-DSAEK) is a recently developed surgical procedure that has shown promising results for the management of various corneal endothelial diseases. OBJECTIVES: To evaluate the outcomes of the UT-DSAEK to the Descemet membrane endothelial keratoplasty (DMEK). DESIGN: A systematic analysis of the studies comparing UT-DSAEK with DMEK by evaluating one or more outcomes (vision, complications, and post-operative endothelial cell counts) was performed. The meta-analysis was done if two or more studies reported a common outcome. METHODS: We used PubMed, EMBASE, and SCOPUS databases to identify articles comparing the outcomes of UT-DSAEK with DMEK and performed a meta-analysis using RevMan, version 5.4. RESULTS: A total of six studies were included in this review (two randomized clinical trials and four non-randomized comparative studies). Our analysis showed the patients who underwent DMEK cases showed better visual outcomes with a mean difference of 0.06 LogMAR (95% CI: 0.04-0.09) in BCVA, albeit with i 2 of 52% (heterogenous values). The evidence was weak, with the most weightage on retrospective studies. UT-DSAEK showed significantly fewer complications such as graft dislocations, with an odds ratio of 0.25 (95% CI: 0.13-0.48). There was no significant difference in the endothelial cell counts with a mean difference of 86.34 (95%CI: -133.09 to -305.77). CONCLUSION: Although the literature is limited on UT-DSAEK with post-operative visual acuity that could be practically at par with DMEK, lesser complication rates and comparable post-operative endothelial cells could be a suitable alternative to DMEK for corneal endothelial pathologies.
The lacrimal gland undergoes significant structural and functional deterioration with aging. Marked with increased inflammation and fibrosis, the aged lacrimal gland is unable to perform its protective function. As a result, the ocular surface becomes highly susceptible to various ocular surface pathologies, including corneal epitheliopathy. We and others have previously shown that mast cells mediate tissue inflammation by recruiting other immune cells. However, despite their well-known characteristics of secreting various inflammatory mediators, whether mast cells contribute to the immune cell aggregation and activation, and acinar dystrophy of the aged lacrimal gland has not been investigated. Here, we demonstrate the role of mast cells in age-related lacrimal gland pathophysiology using mast cell-deficient (cKitw-sh) mice. Our data demonstrated a significant increase in mast cell frequencies and immune cell infiltration in the lacrimal gland of aged mice. Interestingly, mast cell deficiency resulted in a substantial reduction in inflammation and preservation of lacrimal gland structure, suggesting that mast cells mediate the aging process of the lacrimal gland.
Despite extensive study, the mechanisms underlying pain after axonal injury remain incompletely understood. Pain after corneal refractive surgery provides a model, in humans, of the effect of injury to trigeminal afferent nerves. Axons of trigeminal ganglion neurons that innervate the cornea are transected by laser-assisted in situ keratomileusis (LASIK). Although most patients do not experience postoperative pain, a small subgroup develop persistent ocular pain. We previously carried out genomic analysis and determined that some patients with persistent pain after axotomy of corneal axons during refractive surgery carry mutations in genes that encode the electrogenisome of trigeminal ganglion neurons, the ensemble of ion channels and receptors that regulate excitability within these cells, including SCN9A, which encodes sodium channel Nav1.7, a threshold channel abundantly expressed in sensory neurons that has been implicated in a number of pain-related disorders. Here, we describe the biophysical and electrophysiological profiling of the P610T Nav1.7 mutation found in two male siblings with persistent ocular pain after refractive surgery. Our results indicate that this mutation impairs the slow inactivation of Nav1.7. As expected from this proexcitatory change in channel function, we also demonstrate that this mutation produces increased spontaneous activity in trigeminal ganglion neurons. These findings suggest that this gain-of-function mutation in Nav1.7 may contribute to pain after injury to the axons of trigeminal ganglion neurons.NEW & NOTEWORTHY Mechanisms underlying pain after axonal injury remain elusive. A small subgroup of patients experience pain after corneal refractive surgery, providing a human pain model after well-defined injury to axons. Here we analyze a mutation (P610T) in Nav1.7, a threshold sodium channel expressed in nociceptors, found in two siblings with persistent ocular pain after refractive surgery. We show that it impairs channel slow inactivation, thereby triggering inappropriate repetitive activity in trigeminal ganglion axons that signal eye pain.
PURPOSE: To evaluate the retinal vasculature in pediatric patients with X-linked retinoschisis (XLRS) DESIGN: Retrospective consecutive case series SUBJECTS: Pediatric patients with a diagnosis of XLRS who had undergone wide-field fluorescein angiography (FA). METHODS: The electronic medical records of pediatric patients with XLRS at a tertiary referral eye center were reviewed from January 2015 to December 2021. Fluorescein angiography images were reviewed for anomalies of the retinal vasculature. MAIN OUTCOMES: Vascular anomalies on FA were recorded including capillary dropout/ischemia, terminal supernumerary vessels, vascular leakage, abnormal vascular loops, straightening of vessels, aberrant circumferential vessels, and neovascularization. RESULTS: In total, 29 eyes of 15 patients were included in the study (one patient had a phthisical eye). On FA, the most common findings were capillary dropout/ischemia (21 of 29 eyes, 72.4%), terminal supernumerary vessels (21 eyes, 72.4%), abnormal vascular loops (20 eyes, 69%), and vascular leakage (17 eyes, 58.6%). Of the 17 eyes with leakage, the most posterior zone of involvement was Zone 1 in 11 eyes (64.7%) and Zone 2 in 6 eyes (35.3%). All eyes demonstrated at least one vascular anomaly on FA. Among the 29 eyes, 23 (79.3%) demonstrated peripheral bullous schisis or retinal detachment with a mean of 5.6 clock hours of involvement. The presence of either retinal detachment or bullous retinal schisis was associated with the incidence of capillary dropout (91.3% in schisis/RD eyes vs 0% in non-schisis/RD eyes, p<0.001). Among those with retinal detachment or bullous schisis, a higher degree of involvement correlated with more severe capillary dropout (Pearson 0.49, p=0.025). CONCLUSIONS: The present study demonstrates consistent vascular changes in pediatric patients with XLRS using wide-field FA. While the presence of capillary ischemia was associated with the severity of bullous schisis or retinal detachment, other vascular anomalies were seen in patients both with and without peripheral schisis. Though further research is needed to understand the etiology of these vascular anomalies, FA should be considered in the evaluation of these patients.
Singh RB, Parmar UPS, Kahale F, Agarwal A, Tsui E. Reply. Ophthalmology. 2023;
PURPOSE OF REVIEW: We discuss the preoperative, intraoperative, and postoperative considerations for cataract surgery in eyes with high myopia. We also reviewed the recent literature on refractive outcomes and complications of cataract surgery in myopic eyes. RECENT FINDINGS: Several novel intraocular lens (IOL) power calculation formulas have recently been developed to optimize refractive outcomes. Haigis formula is the most accurate among the third-generation IOL formulas. Novel formulas such as Barrett Universal II, Kane, and modified Wang-Koch adjustment for Holladay I formula provide a better refractive prediction compared with old formulas. Intraoperatively, the chopping technique is preferred to minimize pressure on weak zonules and reduce the incidence of posterior capsule rupture. Anterior capsular polishing is recommended to reduce the risk of postoperative capsular contraction syndrome (CCS). Postoperatively, complications such as refractive surprises, intraocular pressure spikes, and CCS remain higher in myopic eyes. Only 63% of myopic patients with axial length more than 26 mm achieve a visual acuity at least 20/40 after cataract surgery, mainly because of coexisting ocular comorbidities. SUMMARY: There are multiple preoperative, intraoperative, and postoperative considerations when performing cataract surgery in myopic eyes. Further research is needed to optimize the refractive outcomes in these eyes and determine the best IOL formula. Surgeons should be adept and knowledgeable with different techniques to manage intraoperative complications.
BACKGROUND: Validated methods to identify neuro-ophthalmologists in administrative data do not exist. The development of such method will facilitate research on the quality of neuro-ophthalmic care and health care utilization for patients with neuro-ophthalmic conditions in the United States. METHODS: Using nationally representative, 20% sample from Medicare carrier files from 2018, we identified all neurologists and ophthalmologists billing at least 1 office-based evaluation and management (E/M) outpatient visit claim in 2018. To isolate neuro-ophthalmologists, the National Provider Identifier numbers of neuro-ophthalmologists in the North American Neuro-Ophthalmology Society (NANOS) directory were collected and linked to Medicare files. The proportion of E/M visits with International Classification of Diseases-10 diagnosis codes that best distinguished neuro-ophthalmic care ("neuro-ophthalmology-specific codes" or NSC) was calculated for each physician. Multiple logistic regression models assessed predictors of neuro-ophthalmology specialty designation after accounting for proportion of ophthalmology, neurology, and NSC claims and primary specialty designation. Sensitivity, specificity, and positive predictive value (PPV) for varying proportions of E/M visits with NSC were calculated. RESULTS: We identified 32,293 neurologists and ophthalmologists who billed at least 1 outpatient E/M visit claim in 2018 in Medicare. Of the 472 NANOS members with a valid individual National Provider Identifier, 399 (84.5%) had a Medicare outpatient E/M visit in 2018. The model containing only the proportion of E/M visits with NSC best predicted neuro-ophthalmology specialty designation (odds ratio 1.05 [95% confidence interval 1.04, 1.05]; P < 0.001; area under the receiver operating characteristic [AUROC] = 0.91). Model predictiveness for neuro-ophthalmology designation was maximized when 6% of all billed claims were for NSC (AUROC = 0.89; sensitivity: 84.0%; specificity: 93.9%), but PPV was low (14.9%). The threshold was unchanged when limited only to neurologists billing ≥1% ophthalmology claims or ophthalmologists billing ≥1% neurology claims, but PPV increased (33.3%). CONCLUSIONS: Our study provides a validated method to identify neuro-ophthalmologists who can be further adapted for use in other administrative databases to facilitate future research of neuro-ophthalmic care delivery in the United States.
Models of object recognition have mostly focused upon the hierarchical processing of objects from local edges up to more complex shape features. An alternative strategy that might be involved in pattern recognition centres around coarse-level contrast features. In humans and monkeys, the use of such features is most documented in the domain of face perception. Given prior suggestions that, generally, rodents might rely upon contrast features for object recognition, we hypothesized that they would pick up the typical contrast features relevant for face detection. We trained rats in a face-nonface categorization task with stimuli previously used in computer vision and tested for generalization with new, unseen stimuli by including manipulations of the presence and strength of a range of contrast features previously identified to be relevant for face detection. Although overall generalization performance was low, it was significantly modulated by contrast features. A model taking into account the summed strength of contrast features predicted the variation in accuracy across stimuli. Finally, with deep neural networks, we further investigated and quantified the performance and representations of the animals. The findings suggest that rat behaviour in visual pattern recognition tasks is partially explained by contrast feature processing.
Choroidal neovascularization (CNV) causes acute vision loss in neovascular age-related macular degeneration (AMD). Genetic variations of the nuclear receptor RAR-related orphan receptor alpha (RORα) have been linked with neovascular AMD, yet its specific role in pathological CNV development is not entirely clear. In this study, we showed that Rora was highly expressed in the mouse choroid compared with the retina, and genetic loss of RORα in Staggerer mice (Rorasg/sg) led to increased expression levels of Vegfr2 and Tnfa in the choroid and retinal pigment epithelium (RPE) complex. In a mouse model of laser-induced CNV, RORα expression was highly increased in the choroidal/RPE complex post-laser, and loss of RORα in Rorasg/sg eyes significantly worsened CNV with increased lesion size and vascular leakage, associated with increased levels of VEGFR2 and TNFα proteins. Pharmacological inhibition of RORα also worsened CNV. In addition, both genetic deficiency and inhibition of RORα substantially increased vascular growth in isolated mouse choroidal explants ex vivo. RORα inhibition also promoted angiogenic function of human choroidal endothelial cell culture. Together, our results suggest that RORα negatively regulates pathological CNV development in part by modulating angiogenic response of the choroidal endothelium and inflammatory environment in the choroid/RPE complex.