Novel Manifestation of Corneal Dystrophy After Keratorefractive Surgery.

PURPOSE: This study aimed to report cases of bilateral corneal Bowman layer deposits in 4 patients with a history of keratorefractive surgery. To our knowledge, this condition has not previously been reported and should be distinguished from granular corneal dystrophy type 2 and other corneal dystrophies. METHODS: We reviewed all available medical records that were collected between January 2010 and December 2021 at a tertiary referral center and performed whole-exome sequencing to provide diagnostic information. RESULTS: Four patients exhibited similar bilateral corneal deposits that were observed more than 10 years after keratorefractive surgery. The patients' ages ranged from 36 to 53 years; 3 of the 4 patients were female. Three patients received laser in situ keratomileusis surgery, and 1 received radial keratotomy. All 4 patients denied having a family history of ocular diseases and reported an uneventful postoperative course. On examination, the best-corrected visual acuity ranged from 6/10 to 6/6 in all 4 patients. Slit-lamp examination revealed bilateral superficial corneal deposits involving the central cornea, and anterior segment optical coherence tomography revealed hyperreflective deposits located in the Bowman layer. Such unique manifestations suggested corneal dystrophy; thus, whole-exome sequencing was performed on all 4 patients. Only 1 patient exhibited a missense mutation in TGFBI . We further analyzed common de novo mutations to explore possible candidate genes associated with this presentation. CONCLUSIONS: We report a rare entity of presumed corneal dystrophy with deposits located in the Bowman layer in 4 patients who had received keratorefractive surgery. Clarifying the underlying pathophysiology and genetic predisposition of this disease may aid in diagnosing and preventing potential complications after keratorefractive surgery.

PREDICTING VISUAL OUTCOME AFTER SURGERY IN PATIENTS WITH IDIOPATHIC EPIRETINAL MEMBRANE USING A NOVEL CONVOLUTIONAL NEURAL NETWORK.

PURPOSE: To develop a deep convolutional neural network that enables the prediction of postoperative visual outcomes after epiretinal membrane surgery based on preoperative optical coherence tomography images and clinical parameters to refine surgical decision making. METHODS: A total of 529 patients with idiopathic epiretinal membrane who underwent standard vitrectomy with epiretinal membrane peeling surgery by two surgeons between January 1, 2014, and June 1, 2020, were enrolled. The newly developed Heterogeneous Data Fusion Net was introduced to predict postoperative visual acuity outcomes (improvement ≥2 lines in Snellen chart) 12 months after surgery based on preoperative cross-sectional optical coherence tomography images and clinical factors, including age, sex, and preoperative visual acuity. The predictive accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve of the convolutional neural network model were evaluated. RESULTS: The developed model demonstrated an overall accuracy for visual outcome prediction of 88.68% (95% CI, 79.0%-95.7%) with an area under the receiver operating characteristic curve of 97.8% (95% CI, 86.8%-98.0%), sensitivity of 87.0% (95% CI, 67.9%-95.5%), specificity of 92.9% (95% CI, 77.4%-98.0%), precision of 0.909, recall of 0.870, and F1 score of 0.889. The heatmaps identified the critical area for prediction as the ellipsoid zone of photoreceptors and the superficial retina, which was subjected to tangential traction of the proliferative membrane. CONCLUSION: The novel Heterogeneous Data Fusion Net demonstrated high accuracy in the automated prediction of visual outcomes after weighing and leveraging multiple clinical parameters, including optical coherence tomography images. This approach may be helpful in establishing personalized therapeutic strategies for epiretinal membrane management.

Ophthalmic characteristics and retinal vasculature changes in Williams syndrome, and its association with systemic diseases.

BACKGROUND: We aim to characterise the ophthalmic findings and retinal vasculature changes in patients with WS, and to analyse the correlation between ophthalmic manifestations and the associated systemic diseases. METHODS: This retrospective case-control study included 27 WS patients and 28 age-matched healthy participants. Stellate pattern of iris, central macular thickness (CMT), foveal width, retinal vessel diameter, superficial vascular density (SVD) of macula and foveal avascular zone (FAZ) were compared between WS patients and healthy participants. RESULTS: Twenty-five patients (93%) had the classic stellate iris presentation. Compared with healthy controls, WS patients had decreased CMT, increased foveal width and a lower SVD of macula (all P < 0.001). Significantly decreased mean retinal arterial (117.9 ± 9.9 µm vs. 133.0 ± 6.7 µm in WS and controls, respectively; p < 0.001) and venous (158.9 ± 11.2 µm vs. 174.0 ± 8.0 µm in WS and controls, respectively; p < 0.001) outer diameters, as well as mean arterial wall thickness (11.2 ± 1.3 µm vs. 12.2 ± 0.8 µm in WS and controls, respectively; p < 0.01) were found in WS. Stellate iris grading was significantly associated with CMT, foveal width, retinal vessel diameter (all p < 0.05), and a significant increase in the odds of having hypertension (Odds ratio (OR), 5.63; P < 0.05). The severity of stellate iris in WS seemed to have the trend of increasing risk of having pulmonary stenosis, tricuspid regurgitation and mitral regurgitation. CONCLUSIONS: This study provides the first in vivo evidence reflecting current knowledge on vessel morphology in WS patients that deficient circumferential growth is the predominant pathophysiologic changes resulting from elastin deficiency. The ophthalmic characteristics may serve as a complementary tool to diagnose and follow-up patients suffering from WS.

Novel mutation of IFT140 in an infant with Mainzer-Saldino syndrome presenting with retinal dystrophy.

A seven-month-old girl presented with bilateral roving nystagmus, hyperopia, and retinal dystrophy, and was brought to our ophthalmology clinic. Visual-evoked potentials (VEPs) were non-recordable in both the eyes. No other systemic symptoms or abnormalities were observed. Whole exome sequencing (WES) identified a compound heterozygous mutation in the IFT140 gene: c.1990G > A (p. Glu664Lys) and c.2214_2217del (p.Asp738GlufsTer47). The genetic results support a diagnosis of Mainzer-Saldino syndrome (MSS). Importantly, c.2214_2217del is a novel mutation in the IFT140 gene. Although the patient presents with isolated retinal dystrophy, it is crucial to monitor renal function overtime. Taken together, our results reinforce the role of IFT140 in syndromic ciliopathies. This report also highlights the role of combined WES approaches in identifying underlying mutations in infants presenting with isolated retinal dystrophy, considering MSS may present differently over time.

Evaluation of a remote telemedicine platform using a novel handheld fundus camera: Physician and patient perceptions from real-world experience.

BACKGROUND: Although teleophthalmology has gained traction in recent years, it is at the center of the coronavirus disease pandemic. However, most hospitals are not ready owing to a severe lack of real-world experience. Furthermore, a limited number of studies have evaluated telemedicine applications on remote islands. This study aimed to evaluate real-world clinical and referral accuracy, image quality, physician-perceived diagnostic certainty, and patient satisfaction with telemedicine eye screening using a novel handheld fundus camera in a rural and medically underserved population. METHODS: This prospective study included 176 eyes from a remote island. All participants underwent a comprehensive ophthalmic examination. Nonmydriatic retinal images obtained using a handheld fundus camera were reviewed by two retinal specialists to determine image quality, diagnosis, and need for referrals. The agreement of diagnosis between image-based assessments was compared with that of binocular indirect ophthalmoscopic assessments. RESULTS: Image quality of fundus photographs was considered acceptable or ideal in 97.7% and 95.5% of eyes assessed by two reviewers, respectively. There was considerable agreement in diagnosis between the indirect ophthalmoscopic assessment and image-based assessment by two reviewers (Cohen's kappa = 0.80 and 0.78, respectively). Likewise, substantial agreement was achieved in the referrals. The sensitivity for referable retinopathy from the two reviewers was 78% (95% confidence interval [CI], 57%-91%) and 78% (95% CI, 57%-91%), whereas specificity was 99% (95% CI, 95%-99%] and 98% (95% CI, 93%-99%), respectively. For physicians' perceived certainty of diagnosis, 93.8% and 90.3% were considered either certain or reliable. Overall, 97.4% of participants were satisfied with their experiences and greatly valued the telemedicine services. CONCLUSION: Novel fundus camera-based telemedicine screening demonstrated high accuracy in detecting clinically significant retinopathy in real-world settings. It achieved high patient satisfaction and physician-perceived certainty in diagnosis with reliable image quality, which may be scaled internationally to overcome geographical barriers under the global pandemic.

Retinal Microvascular Changes in Mild Cognitive Impairment and Alzheimer's Disease: A Systematic Review, Meta-Analysis, and Meta-Regression.

Background: The remarkable increase in prevalence and significant morbidity of neurodegenerative diseases pose a tremendous burden for the health care system. Changes in retinal microvasculature metrics associated with Alzheimer's disease (AD) and mild cognitive impairment (MCI) may provide opportunities for early diagnosis and intervention. However, the role of retinal vascular biomarkers remains controversial. We aim to perform a systematic review, meta-analysis and meta-regression to evaluate the comprehensive retinal microvasculature changes in patients with AD and MCI. Methods: We conducted a literature search on PubMed, MEDLINE, and EMBASE to identify studies published before May 2021 which assessed the measurements of optical coherence tomography angiography (OCTA) between AD, MCI with healthy control eyes, including foveal avascular zone (FAZ), vessel density (VD) of peripapillary, superficial and deep capillary plexus, and choroidal thickness using a random-effect model. We also performed meta-regression and subgroup analysis and assessed heterogeneity and publication bias to evaluate potential sources of bias. Results: Compared with control eyes, VD of superficial capillary plexus was significantly lower in AD [standardized mean difference (SMD): -0.48; 95% CI (-0.70 to -0.27); p = 0.04] and MCI eyes [SMD: -0.42; 95% CI (-0.81 to -0.03); p = 0.03], as well as reduced VD of deep capillary plexus [SMD: -1.19; 95% CI (-2.00 to -0.38]; p < 0.001], [SMD: -0.53; 95% CI (-0.85 to -0.22); p < 0.001]. FAZ was significantly enlarged in AD eyes [SMD: 0.54; 95% CI (0.09 to 0.99); p = 0.02]. The meta-regression analysis showed that the OCTA machine type and macular scan size significantly influenced the variation of VD and FAZ between AD and control eyes (p < 0.05). Conclusion: Our results highlight the potential of OCTA as a biomarker to detect early microvasculature deficits in AD and MCI. Notably, the macular scan size and different OCTA machine type could explain the heterogeneity observed in literatures. This information might be useful for future longitudinal study design to evaluate the role of OCTA in monitoring disease progression and treatment efficacy.

Prediction of treatment outcome in neovascular age-related macular degeneration using a novel convolutional neural network.

While prognosis and risk of progression are crucial in developing precise therapeutic strategy in neovascular age-related macular degeneration (nAMD), limited predictive tools are available. We proposed a novel deep convolutional neural network that enables feature extraction through image and non-image data integration to seize imperative information and achieve highly accurate outcome prediction. The Heterogeneous Data Fusion Net (HDF-Net) was designed to predict visual acuity (VA) outcome (improvement ≥ 2 line or not) at 12th months after anti-VEGF treatment. A set of pre-treatment optical coherence tomography (OCT) image and non-image demographic features were employed as input data and the corresponding 12th-month post-treatment VA as the target data to train, validate, and test the HDF-Net. This newly designed HDF-Net demonstrated an AUC of 0.989 (95% CI 0.970-0.999), accuracy of 0.936 [95% confidence interval (CI) 0.889-0.964], sensitivity of 0.933 (95% CI 0.841-0.974), and specificity of 0.938 (95% CI 0.877-0.969). By simulating the clinical decision process with mixed pre-treatment information from raw OCT images and numeric data, HDF-Net demonstrated promising performance in predicting individualized treatment outcome. The results highlight the potential of deep learning to simultaneously process a broad range of clinical data to weigh and leverage the complete information of the patient. This novel approach is an important step toward real-world personalized therapeutic strategy for typical nAMD.

Chlorhexidine in the treatment of microsporidial stromal keratitis and the effect of host immunity: A case series and literature review.

Microsporidial stromal keratitis is an increasingly well-known vision-threatening disease. A large proportion of cases are initially misdiagnosed as herpes simplex keratitis and treated with topical steroids. In most of such cases, medical treatment failed, and corneal transplantation was required. This study reported the results of 0.02% topical chlorhexidine used to treat three cases of microsporidial stromal keratitis and reviewed the literature on the outcomes of microsporidial stromal keratitis treatment. In the first case, histopathology of a specimen from penetrating keratoplasty (PK) revealed severe chronic inflammation involving the entire stromal layer but no microorganism activity after the application of topical chlorhexidine for 10 months. The second case exhibited complete resolution of keratitis after topical chlorhexidine. The patient in the third case did not respond to medical treatment, and therapeutic PK was performed. Histopathological examination revealed numerous microsporidial spores that had colonized in the mid and deep stroma, where few inflammatory cells were observed. These findings explain the variable microsporidial susceptibility to chlorhexidine, suggesting the crucial role of host immunity. In cases of host immunity, topical chlorhexidine may represent a promising option for the treatment of microsporidial stromal keratitis.

Plug-related canaliculitis: a rare or underdiagnosed disease?

CLINICAL RELEVANCE: Conjunctivitis, chalazion and blepharitis are routinely managed by optometrists. However, it is especially important to consider the diagnosis of canaliculitis in patients with chronic or recurrent conditions. BACKGROUND: This study aimed to report the clinical features, radiological findings and treatment outcomes in patients with plug-related canaliculitis. METHODS: This retrospective study included patients with canaliculitis secondary to plug insertion between 2007 and 2020. All data regarding epidemiological characteristics, clinical presentation, isolated microorganisms, computed tomography imaging findings, treatment, and outcomes were analysed. RESULTS: A total of 20 plug-related canaliculitis from 19 patients (18.3%) among all 109 cases of canaliculitis were identified. All patients with plug-related canaliculitis were females with a past history of lacrimal plug insertion for dry eye (mean age: 58.2 years). Most patients were initially treated as conjunctivitis with the mean time lapse to a diagnosis of 5.2 months. The average time from plug insertion to onset of symptoms was 5.1 years. Eighteen patients underwent canaliculotomy, and one patient received lacrimal irrigation. Plugs were identified in 18 cases, with SmartPlug in 13 cases (72%), followed by EaglePlugTM (two cases), Herrick Lacrimal Plug (two cases), and migrated FCI Painless Plug (1 case). Cultures of discharge, concretions, and/or infected plugs mostly revealed Pseudomonas aeruginosa (42%). Orbital computed tomography in four cases with SmartPlug revealed central radiolucency with surrounding soft-tissue enhancement. No recurrent canaliculitis was observed throughout a mean follow-up period of 13.7 months. No patient needed re-plugging after canaliculotomy and plug removal, with only one required additional lubricants for recurrent dry eye. CONCLUSION: Plug-related canaliculitis is often underdiagnosed due to late onset and similar symptoms to common ocular diseases. Awareness of plug insertion history as well as meticulous removal of the plug, concretion and/or granulation tissue is important for early diagnosis and to ensure a good outcome.

Risk of obstructive sleep apnea in patients with Sjögren syndrome and Behçet's disease: a nationwide, population-based cohort study.

PURPOSE: Patients with obstructive sleep apnea (OSA) have a higher risk of Behçet's disease (BD) and Sjögren syndrome (SS). However, the bidirectional relationship between these autoimmune diseases and OSA is unclear. We investigated the relationship between autoimmune diseases (SS and BD) and OSA. METHODS: SS and BD patients were identified through the Taiwan National Health Insurance Research Database from 2002 to 2012. Patients with SS or BD were matched according to age and sex with a control group in a ratio of 1:4. The study included 12,926 patients with SS and 51,704 non-SS controls. Similarly, 1221 patients with BD were matched with 4884 non-BD controls. We used a Cox regression model, stratified by age, gender, and comorbidities, to assess the risk of OSA. RESULTS: OSA was diagnosed in 0.61% of the SS cohort and 1.23% of the BD cohort. The higher overall risk for OSA was observed significantly in patients with SS than in controls (adjusted hazard ratio [HR] = 2.48, 95% confidence interval [CI] = 1.89-3.24). The higher risk was also observed significantly in BD patients than in controls (HR = 1.99, 95% CI = 1.06-3.72). Furthermore, men with SS or BD exhibited HR of 2.62 (95% CI 1.89 to 3.62) and 6.40 (95% CI 2.96 to 13.84) for developing OSA, respectively. CONCLUSION: Risk of OSA was significantly elevated in SS or BD patients compared with controls. Further study is warranted to elucidate underlying mechanisms.

Surgical adhesives in ophthalmology: history and current trends.

Tissue adhesives are gaining popularity in ophthalmology, as they could potentially reduce the complications associated with current surgical methods. An ideal tissue adhesive should have superior tensile strength, be non-toxic and anti-inflammatory, improve efficiency and be cost-effective. Both synthetic and biological glues are available. The primary synthetic glues include cyanoacrylate and the recently introduced polyethylene glycol (PEG) derivatives, while most biological glues are composed of fibrin. Cyanoacrylate has a high tensile strength, but rapidly polymerises upon contact with any fluid and has been associated with histotoxicity. Fibrin induces less toxic and inflammatory reactions, and its polymerisation time can be controlled. Tensile strength studies have shown that fibrin is not as strong as cyanoacrylate. While more research is needed, PEG variants currently appear to have the most promise. These glues are non-toxic, strong and time-effective. Through MEDLINE and internet searches, this paper presents a systematic review of the current applications of surgical adhesives to corneal, glaucoma, retinal, cataract and strabismus surgeries. Our review suggests that surgical adhesives have promise to reduce problems in current ophthalmic surgical procedures.

Use and Yield of Baseline Imaging and Laboratory Testing in Stage II Breast Cancer.

BACKGROUND: Despite guideline recommendations, baseline laboratory testing and advanced imaging are widely ordered in clinical practice to stage asymptomatic patients with clinical stage II breast cancer (BC). MATERIALS AND METHODS: A retrospective study at two academic centers in Boston, Massachusetts, between 2006 and 2007 explored the use, results, and implications of laboratory tests, tumor markers, and imaging in patients with clinical stage II BC. RESULTS: Among 411 patients, 233 (57%) had liver function testing, 134 (33%) had tumor marker tests, and 237 (58%) had computed tomography (CT) as part of their initial diagnostic workup. Median age was 52 (range, 23-90 years). On multivariable analysis, young age, more advanced stage, and tumor subtype (human epidermal growth receptor-positive [HER2+] and triple-negative breast cancer [TNBC]) were significantly associated with baseline CT. The rate of detection of true metastatic disease with use of baseline staging imaging was 2.1% (95% confidence interval, 0.7%-5%). It was 2.2% (3 of 135) for estrogen receptor/progesterone receptor-positive disease, 1.9% (1 of 54) for HER2+ disease, and 2.1% (1 of 48) for TNBC. At 5 years of follow-up, 46 of 406 patients were diagnosed with metastatic breast cancer. Thirty-four of 46 (73.9%) who developed recurrent disease had imaging at their initial diagnosis, and of these, five had abnormalities on their initial imaging that was correlated with where they developed metastatic disease. CONCLUSION: In this cohort of women with stage II BC, staging imaging at diagnosis had a low yield in detecting distant metastases (2.1%). The detection rate was not higher with HER2+ disease or TNBC, despite the trend that patients with these subtypes were more likely to undergo imaging. IMPLICATIONS FOR PRACTICE: Despite guideline recommendations, asymptomatic patients with stage II breast cancer (BC) often undergo staging imaging with computed tomography, bone scanning, or positron emission tomography. Physicians have often reported that they order imaging despite recommendations because they believe that younger patients or patients with more aggressive BC phenotypes, such as human epidermal receptor 2-positive BC or triple-negative BC, benefit from staging imaging. In this cohort of women younger than those in prior studies, the yield of detecting distant metastatic disease in patients with clinical stage II BC was very low and the detection rate was not higher in the presence of HER2-positive or triple-negative BC.