Publications

2020

Kempen J, Van Natta M, Friedman D, Altaweel M, Ansari H, Dunn J, Elner S, Holbrook J, Lim L, Sugar E, Jabs D, Group MUST (MUST) TF up SR. Incidence and Outcome of Uveitic Glaucoma in Eyes With Intermediate, Posterior, or Panuveitis Followed up to 10 Years After Randomization to Fluocinolone Acetonide Implant or Systemic Therapy. Am J Ophthalmol. 2020;219:303–316.
PURPOSE: To evaluate long-term risk and outcomes of glaucoma in eyes with intermediate, posterior, and panuveitis managed with systemic or fluocinolone acetonide (0.59 mg, "implant") therapy. DESIGN: Prospective Follow-up of the Multicenter Uveitis Steroid Treatment (MUST) Clinical Trial Cohort. METHODS: Patients with intermediate, posterior, or panuveitis randomized to implant or systemic therapy (corticosteroid plus immunosuppression in >90%) were followed prospectively for glaucoma incidence and outcome. RESULTS: Among 405 uveitic at-risk eyes of 232 patients (median follow-up = 6.9 years), 40% (79/196) of eyes assigned and treated with implant and 8% (17/209) of eyes assigned and treated with systemic therapy (censoring eyes receiving an implant on implantation) developed glaucoma (hazard ratio [HR] = 5.9, 95% confidence interval [CI] 3.2, 10.8; P < .001). Adjustment for intraocular pressure (IOP) elevation during follow-up only partially mitigated the association of implant treatment with glaucoma incidence: HR = 3.1 (95% CI 1.6, 6.0); P = .001. Among 112 eyes of 83 patients developing glaucoma, the 5-year cumulative incidence following diagnosis of sustained (2 or more consecutive visits) worsening of mean deviation by ≥6 dB was 20% (95% CI 12%, 33%); 5-year cumulative incidence of sustained worsening of cup-to-disc ratio by ≥0.2 was 26% (95% CI 17%, 39%). CONCLUSIONS: The implant has substantially higher risk of glaucoma than systemic therapy, a difference not entirely explained by posttreatment IOP elevation. Management of IOP elevation was effective in preventing worsening of glaucoma for the large majority of cases, but even under expert clinical management, some glaucoma worsened. Uveitis cases should be monitored carefully for IOP elevation and glaucoma indefinitely.
Thyroid eye disease (TED) is an autoimmune inflammatory disease of the orbit and the most common extrathyroidal manifestation of Graves disease. The release of pro-inflammatory cytokines is associated with inflammation of the ocular surface and lacrimal gland along with periorbital skin erythema and edema. Resultant tissue remodeling, fibrosis, and fat deposition can impart permanent physical changes to the ocular adnexa with effects on function and cosmesis. These changes occur in the active phase of disease, and it is during this time that steroids are often relied on to help alleviate symptoms. Due to the common and predictable side effects of long-term and high-dose steroid use, there has been a continuous effort to find alternative steroid-sparing medical management options for TED. This review highlights the various research studies that support the use of these medications.
Kegeles E, Naumov A, Karpulevich E, Volchkov P, Baranov P. Convolutional Neural Networks Can Predict Retinal Differentiation in Retinal Organoids. Front Cell Neurosci. 2020;14:171.
We have developed a deep learning-based computer algorithm to recognize and predict retinal differentiation in stem cell-derived organoids based on bright-field imaging. The three-dimensional "organoid" approach for the differentiation of pluripotent stem cells (PSC) into retinal and other neural tissues has become a major strategy to recapitulate development. We decided to develop a universal, robust, and non-invasive method to assess retinal differentiation that would not require chemical probes or reporter gene expression. We hypothesized that basic-contrast bright-field (BF) images contain sufficient information on tissue specification, and it is possible to extract this data using convolutional neural networks (CNNs). Retina-specific Rx-green fluorescent protein mouse embryonic reporter stem cells have been used for all of the differentiation experiments in this work. The BF images of organoids have been taken on day 5 and fluorescent on day 9. To train the CNN, we utilized a transfer learning approach: ImageNet pre-trained ResNet50v2, VGG19, Xception, and DenseNet121 CNNs had been trained on labeled BF images of the organoids, divided into two categories (retina and non-retina), based on the fluorescent reporter gene expression. The best-performing classifier with ResNet50v2 architecture showed a receiver operating characteristic-area under the curve score of 0.91 on a test dataset. A comparison of the best-performing CNN with the human-based classifier showed that the CNN algorithm performs better than the expert in predicting organoid fate (84% vs. 67 ± 6% of correct predictions, respectively), confirming our original hypothesis. Overall, we have demonstrated that the computer algorithm can successfully recognize and predict retinal differentiation in organoids before the onset of reporter gene expression. This is the first demonstration of CNN's ability to classify stem cell-derived tissue .
Wolkow N, Jakobiec F, Gragoudas E. LONG-TERM OBSERVATION OF MULTIFOCAL METASTATIC INTRAOCULAR CARCINOID WITH ACQUIRED IRIS HETEROCHROMIA. Retin Cases Brief Rep. 2020;14(3):265–267.
BACKGROUND/PURPOSE: To report a unique case of a pulmonary carcinoid tumor unilaterally metastatic to the iris and ciliary body and bilaterally to the choroid that was conservatively followed. METHODS: A 46-year-old woman presented with bilateral choroidal lesions and a left iris tumor. Ultrasound biomicroscopy disclosed a ciliary body component. A diagnosis of metastatic carcinoid tumor was made based on the clinical features. Rather than an excision, photodynamic therapy, or radiation treatment, as has been reported in all previous cases of carcinoid tumor metastatic to the iris, the patient was observed. RESULTS: Excellent vision was maintained for 8 years. The iris tumor gradually enlarged, but the choroidal lesions remained unchanged. The iris with the carcinoid tumor gradually acquired a brown pigmentation; this is the first reported case of acquired iris heterochromia in the setting of carcinoid tumor. CONCLUSION: We conclude, in cases of metastatic carcinoid in which visual acuity is excellent and the patient is asymptomatic, that observation of the ocular lesions is an acceptable course of action. The iris heterochromia is believed to have been caused by secretory factors produced by the tumor.
Nartker M, Alaoui-Soce A, Wolfe J. Visual search errors are persistent in a laboratory analog of the incidental finding problem. Cogn Res Princ Implic. 2020;5(1):32.
When radiologists search for a specific target (e.g., lung cancer), they are also asked to report any other clinically significant "incidental findings" (e.g., pneumonia). These incidental findings are missed at an undesirably high rate. In an effort to understand and reduce these errors, Wolfe et al. (Cognitive Research: Principles and Implications 2:35, 2017) developed "mixed hybrid search" as a model system for incidental findings. In this task, non-expert observers memorize six targets: half of these targets are specific images (analogous to the suspected diagnosis in the clinical task). The other half are broader, categorically defined targets, like "animals" or "cars" (analogous to the less well-specified incidental findings). In subsequent search through displays for any instances of any of the targets, observers miss about one third of the categorical targets, mimicking the incidental finding problem. In the present paper, we attempted to reduce the number of errors in the mixed hybrid search task with the goal of finding methods that could be deployed in a clinical setting. In Experiments 1a and 1b, we reminded observers about the categorical targets by inserting non-search trials in which categorical targets were clearly marked. In Experiment 2, observers responded twice on each trial: once to confirm the presence or absence of the specific targets, and once to confirm the presence or absence of the categorical targets. In Experiment 3, observers were required to confirm the presence or absence of every target on every trial using a checklist procedure. Only Experiment 3 produced a marked decline in categorical target errors, but at the cost of a substantial increase in response time.
Solyman O, Elhusseiny A, Hashem H. Severe bilateral ankyloblepharon filiforme adnatum. J AAPOS. 2020;
We present a case of bilateral ankyloblepharon filiforme adnatum in 1-day-old girl and describe our surgical approach. The bands connecting the upper and lower eyelids of both eyes were severed using blunt scissors. Point bleeding at the cut bands stopped in 1-2 minutes, without the need for cauterization or compression. The patient was able to open her eyes shortly after the procedure, as she woke up from anesthesia. Examination under general anesthesia showed normal eye examination appropriate for age. Postoperatively, the patient maintained open palpebral fissures. Visual development over 3 years' follow-up was normal.
Hernandez-Llamas S, Paz-Ramos AK, Marcos-Gonzalez P, Amparo F, Garza-Leon M. Symptoms of ocular surface disease in construction workers: comparative study with office workers. BMC Ophthalmol. 2020;20(1):272.
BACKGROUND: To investigate and contrast the prevalence of dry eye symptoms in construction workers and office workers using the OSDI questionnaire. METHODS: A cross-sectional, observational study was conducted using the OSDI questionnaire to evaluate dry eye symptoms and associated risk factors. Sampled size calculation with a power of 80% and a 95% degree of confidence suggested the inclusion of 298 participants. RESULTS: We studied 304 subjects (149 construction workers and 155 office workers). More than half (55%) of the participants presented dry eye symptoms (OSDI > 12). The average OSDI score was 21.30 ± 22.20 points, being lower in the group of construction workers (12.45 ± 17.50) than in-office workers (28.51 ± 22.99) (p <  0.001). Considering participants who had moderate and severe symptoms (23 to 100 points in OSDI), office workers presented dry eye symptoms 4.15 times more frequently than construction workers (OR 4.15, 95% CI 2.52, 6.85). Women presented statistical evidence of higher OSDI scores than men (32.47 ± 23.72 vs. 14.87 ± 18.48, respectively). CONCLUSIONS: construction workers have four times less risk of presenting dry eye symptoms than people working in the average office space. This highlights the pernicious effects on the ocular surface of the office environment, which poses a significant risk for the development or worsening of dry eye symptoms.
Ashofteh Yazdi, Melchor, Torres, Faris, Callejas, Gonzalez-Andrades, Rus. Characterization of non-linear mechanical behavior of the cornea. Sci Rep. 2020;10(1):11549.
The objective of this study was to evaluate which hyperelastic model could best describe the non-linear mechanical behavior of the cornea, in order to characterize the capability of the non-linear model parameters to discriminate structural changes in a damaged cornea. Porcine corneas were used, establishing two different groups: control (non-treated) and NaOH-treated (damaged) corneas (n = 8). NaOH causes a chemical burn to the corneal tissue, simulating a disease associated to structural damage of the stromal layer. Quasi-static uniaxial tensile tests were performed in nasal-temporal direction immediately after preparing corneal strips from the two groups. Three non-linear hyperelastic models (i.e. Hamilton-Zabolotskaya model, Ogden model and Mooney-Rivlin model) were fitted to the stress-strain curves obtained in the tensile tests and statistically compared. The corneas from the two groups showed a non-linear mechanical behavior that was best described by the Hamilton-Zabolotskaya model, obtaining the highest coefficient of determination (R > 0.95). Moreover, Hamilton-Zabolotskaya model showed the highest discriminative capability of the non-linear model parameter (Parameter A) for the tissue structural changes between the two sample groups (p = 0.0005). The present work determines the best hyperelastic model with the highest discriminative capability in description of the non-linear mechanical behavior of the cornea.