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Thomas A Lazzarini,1 Hasenin Al-khersan,1 Nimesh A Patel,1 Nicolas A Yannuzzi,1 Jaime D Martinez,1 Diego Altamirano,1 Lizt K Torres,2 Darlene Miller,1 Juan F Batlle,1,2 Guillermo Amescua,1 Harry W Flynn Jr1 1Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami, Miller School of Medicine, Miami, FL, 33136, USA; 2Laser Center, Santo Domingo, Dominican RepublicCorrespondence: Thomas A LazzariniDepartment of Ophthalmology, Bascom Palmer Eye Institute, University of Miami, Miller School of Medicine, 900 NW 17th Street, Miami, FL 33136, USATel +1 305 326-6118Fax +1 305 326-6417Email txl564@miami.eduAbstract: A 79-year-old man presented to a tertiary referral center from the Dominican Republic with an opaque corneal graft and a diagnosis of chronic, recurrent culture-positive Achromobacter xylosoxidans endophthalmitis of the left eye. The patient had a history of penetrating keratoplasty for Fuchs’ dystrophy and had undergone multiple intraocular surgeries including pars plana vitrectomy and anterior chamber wash out for the diagnosis and management of chronic endophthalmitis. After being referred, the patient underwent a third PKP, removal of his intraocular lens (IOL), capsulectomy, and injection of intravitreal antibiotics. All surgical specimens demonstrated the growth of A. xylosoxidans. Five months after surgery, the graft remained clear without evidence of infection and best-corrected visual acuity was 20/350.Keywords: endophthalmitis, Achromobacter xylosoxidans, ophthalmlology, postoperative endophthalmitis, ophthalmic infection

Jeffrey C Peterson,1,2 Heather Durkee,1,2 Darlene Miller,3,4 Jorge Maestre-Mesa,3,4 Alejandro Arboleda,1 Mariela C Aguilar,1 Nidhi Relhan,1 Harry W Flynn Jr,3 Guillermo Amescua,3 Jean-Marie Parel,1–3 Eduardo Alfonso3 1Ophthalmic Biophysics Center, Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA; 2Department of Biomedical Engineering, University of Miami, Coral Gables, FL, USA; 3Anne Bates Leach Eye Center, Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA; 4Ocular Microbiology Laboratory, Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA Purpose: To characterize the molecular, epidemiological, and resistance profiles of methicillin-resistant (MRSA) and methicillin-susceptible (MSSA) keratitis isolates.Patients and methods: We used a combination of standard microbiological techniques and DNA microarray analysis to characterize the molecular and antibiotic resistance profiles of 75 Staphylococcus aureus keratitis isolates collected over an 11-year period (2006–2016).Results: Two major USA clonal complexes (CC), CC5 (n=30, 40%) and CC8 (n=28, 37.3%), accounted for 77.3% of the collected S. aureus isolates. USA100, traditionally healthcare associated (n=18/47, 38.3%), and USA300, traditionally community associated (n=12/47, 25.5%), were the dominant MRSA strains. Four (22.2%) of the USA100 MRSA isolates were recovered from patients with no prior healthcare exposure. Eleven (91.7%) of the USA300 isolates were recovered from patients with documented healthcare risk factors. MSSA isolates were polyclonal (n=13). Ninety-three percent of MSSA infections were of healthcare origin. Thirty-seven of 61 (60.6%) healthcare- and 11 of 14 (78.6%) community-associated strains were resistant to three or more antibiotic classes. Sixty-eight percent (n=51) of isolates harbored three of more resistance determinants (genes). The Panton-Valentine Leucocidin gene was detected in 11 (14.7%) of the study isolates. The majority (72.7%) of the strains were members of the USA300 MRSA clone.Conclusion: Clonal complexes CC5 and CC8 were the most frequent clones detected among both the MSSA and the MRSA keratitis isolates. USA100 and USA300 clones were the dominant MRSA genotypes. The USA300 MRSA clone has become a leading cause of healthcare-associated keratitis in South Florida. The USA100 MRSA clone has emerged as an increasing cause of community-associated corneal infections in our outpatient population. This shifting epidemiology coupled with the increasing prevalence of multidrug resistance among both MSSA and MRSA keratitis is a cause of concern. Keywords: MRSA, MSSA, DNA microarray, USA100, USA300, clones

Allister Gibbons,1 Ella H Leung,1 Luis J Haddock,1 Carlos A Medina,1 Viviana Fernandez,2 Jean-Marie A Parel,1,2 Heather A Durkee,2 Guillermo Amescua,1 Eduardo C Alfonso,1 Victor L Perez1,3 1Bascom Palmer Eye Institute/University of Miami Miller School of Medicine, Miami, FL, 2Ophthalmic Biophysics Center, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, 3Ocular Surface Center, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA Purpose: To determine the indications, long-term clinical and visual outcomes, and complications of the aphakic snap-on type I Boston keratoprosthesis (KPro). Design: Retrospective, non-comparative case series. Methods: Forty-five eyes of 43 patients with type I aphakic snap-on KPros with at least 1 year of follow-up were included. The past medical histories, preoperative indications, best-corrected visual acuities (BCVAs), postoperative complications, and retention rates were analyzed. Results: The most common indication for KPro implantation was a failed corneal graft (89%). The mean preoperative BCVA was count fingers–hand motion (2.14±0.45 logarithm of minimum angle of resolution [logMAR]), which initially improved to 20/200 (1.04±0.85 logMAR; P

Marwan Raymond Atallah, Sotiria Palioura, Victor L Perez, Guillermo Amescua Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA Abstract: Regeneration of the corneal surface after an epithelial insult involves division, migration, and maturation of a specialized group of stem cells located in the limbus. Several insults, both intrinsic and extrinsic, can precipitate destruction of the delicate microenvironment of these cells, resulting in limbal stem cell deficiency (LSCD). In such cases, reepithelialization fails and conjunctival epithelium extends across the limbus, leading to vascularization, persistent epithelial defects, and chronic inflammation. In partial LSCD, conjunctival epitheliectomy, coupled with amniotic membrane transplantation, could be sufficient to restore a healthy surface. In more severe cases and in total LSCD, stem cell transplantation is currently the best curative option. Before any attempts are considered to perform a limbal stem cell transplantation procedure, the ocular surface must be optimized by controlling causative factors and comorbid conditions. These factors include adequate eyelid function or exposure, control of the ocular surface inflammatory status, and a well-lubricated ocular surface. In cases of unilateral LSCD, stem cells can be obtained from the contralateral eye. Newer techniques aim at expanding cells in vitro or in vivo in order to decrease the need for large limbal resection that may jeopardize the “healthy” eye. Patients with bilateral disease can be treated using allogeneic tissue in combination with systemic immunosuppressive therapy. Another emerging option for this subset of patients is the use of noncorneal cells such as mucosal grafts. Finally, the use of keratoprosthesis is reserved for patients who are not candidates for any of the aforementioned options, wherein the choice of the type of keratoprosthesis depends on the severity of the disease. In summary, limbal stem cell transplantation improves both vision and quality-of-life in patients with ocular surface disorders associated with LSCD, and overall, the use of autologous tissue offers the best results. Future studies aim at improving cellular expansion and finding different sources of stem cells. Keywords: limbal stem cell deficiency (LSCD), simple limbal epithelial transplantation (SLET), cultivated limbal epithelial transplantation (CLET), keratolimbal allograft (KLAL)

Sotiria Palioura, Christopher R Henry, Guillermo Amescua, Eduardo C AlfonsoDepartment of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA Abstract: Bacterial keratitis can lead to severe visual impairment from corneal ulceration, subsequent scarring, and possible perforation. The mainstay of treatment is topical antibiotics, whereas the use of adjunctive topical corticosteroid drops remains a matter of debate. Herein, we review the rationale for and against the use of topical corticosteroids and we assess their effectiveness and safety in the published randomized controlled trials that have evaluated their role as adjunctive therapy for bacterial corneal ulcers. In the largest study to date, the Steroids for Corneal Ulcers Trial, topical corticosteroid drops were neither helpful nor harmful for the 500 participants as a whole. However, subgroup analyses suggested that topical corticosteroids may be beneficial upon early administration (within 2–3 days after starting antibiotics) for more central corneal ulcers with poorer vision at presentation, for invasive Pseudomonas strains, and for non-Nocardia ulcers. These results are discussed within the limitations of the study.Keywords: topical corticosteroids, corneal ulcer, eye infection, antibiotic, endophthalmitis, perforation

Infectious keratitis represents a significant cause of ocular morbidity in the United States. The work-up and treatment of presumed infectious keratitis (PIK) has changed in the past two decades. The development of newer topical antibiotics has enabled broad-spectrum antibiotic coverage with good tissue penetration. The majority of PIK cases respond well to this strategy. The small numbers of cases that do not respond to the treatment are the cases that offer a diagnostic and therapeutic challenge. This review will describe different algorithms that can be followed for the successful management of patients with difficult or progressive PIK. These algorithms are based on scientific work and on our empirical clinical experience. The review will also present three different clinical cases of PIK that were managed according to the algorithms presented in this review. [ABSTRACT FROM AUTHOR]

Aims: To develop a generative adversarial network (GAN) capable of generating realistic high-resolution anterior segment optical coherence tomography (AS-OCT) images., Methods: This study included 142 628 AS-OCT B-scans from the American University of Beirut Medical Center. The Style and WAvelet based GAN architecture was trained to generate realistic AS-OCT images and was evaluated through the Fréchet Inception Distance (FID) Score and a blinded assessment by three refractive surgeons who were asked to distinguish between real and generated images. To assess the suitability of the generated images for machine learning tasks, a convolutional neural network (CNN) was trained using a dataset of real and generated images over a classification task. The generated AS-OCT images were then upsampled using an enhanced super-resolution GAN (ESRGAN) to achieve high resolution., Results: The generated images exhibited visual and quantitative similarity to real AS-OCT images. Quantitative similarity assessed using FID scored an average of 6.32. Surgeons scored 51.7% in identifying real versus generated images which was not significantly better than chance (p value >0.3). The CNN accuracy improved from 78% to 100% when synthetic images were added to the dataset. The ESRGAN upsampled images were objectively more realistic and accurate compared with traditional upsampling techniques by scoring a lower Learned Perceptual Image Patch Similarity of 0.0905 compared with 0.4244 of bicubic interpolation., Conclusions: This study successfully developed and leveraged GANs capable of generating high-definition synthetic AS-OCT images that are realistic and suitable for machine learning and image analysis tasks., Competing Interests: Competing interests: DZR is a consultant for Carl Zeiss Meditec (Carl Zeiss Meditec AG, Jena, Germany). DZR is also a consultant for CSO Italia (Florence, Italy) and has a proprietary interest in the Artemis technology (ArcScan Inc, Golden, Colorado) through patents administered by the Cornell Center for Technology Enterprise and Commercialization (CCTEC), Ithaca, New York. The remaining authors have no proprietary or financial interest in the materials presented herein., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To evaluate the incidence of chronic cicatrizing conjunctivitis (CCC) and its associated risk factors in the context of chronic ocular graft-vs-host disease (coGVHD)., Methods: A retrospective chart review of individuals diagnosed with coGVHD following hematopoietic stem cell transplantation (HSCT) who were seen at the Bascom Palmer Eye Institute between May 2010 and November 2021 was performed. Data regarding baseline demographic characteristics, systemic co-morbidities, lid margin abnormalities, ocular cicatricial changes, transplant information, immunosuppressive therapy, and GVHD severity assessments were collected. The incidence of cicatricial conjunctivitis was estimated with Kaplan-Meier survival analysis. A Cox regression model was used to assess the contribution of demographic and systemic variables to the development of CCC., Results: 167 individuals were included (53.9 ± 14.7 years old; 60.5 % male). 65 individuals presented with features suggestive of CCC an average of 60.9 ± 53.8 months after HSCT, with 60-month and 120-month incidences of 29.3 % and 48.9 %, respectively. Multivariable analysis demonstrated that age younger than 50 at the time of the first eye visit was associated with a higher chance of CCC development (Hazard Ratio (HR): 2.14, 95 % Confidence Interval (CI): 1.16-3.97, p = 0.02)., Conclusion: Clinically detected cicatrizing conjunctivitis is an ocular manifestation of coGVHD, with an incidence that increases over time. Younger individuals may be at higher risk for CCC development., (Published by Elsevier Inc.)

Purpose: To report a successfully managed case of idiopathic Fusarium sclerouveitis in a healthy patient with no identifiable risk factors., Methods: We describe a case of a 79-year-old man who presented with right-sided eye, facial, and head pain. Initial examination revealed temporal scleral thinning, inflammation, and anterior chamber cell/flare. Cultures were positive for Fusarium species., Results: The patient was treated with sub-Tenon amphotericin, intrascleral voriconazole, surgical debridement, Rose Bengal photodynamic therapy, systemic voriconazole and posaconazole, and topical natamycin. The infection resolved and the patient's visual acuity improved to 20/40., Conclusions: Fusarium sclerouveitis can occur without clear risk factors. This case highlights the importance of an aggressive, multimodal treatment approach for successful management., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The Steroids and Cross-linking for Ulcer Treatment Trial is an NIH-funded international, randomized, double-masked, sham and placebo-controlled clinical trial to determine the benefit of adjunctive corneal cross-linking with riboflavin and/or topical difluprednate in addition to topical antibiotic drops for treatment of smear-positive bacterial ulcers. The purpose of this study was to explore the baseline characteristics for infection of patients enrolled, and the ocular comorbidities of patients screened for inclusion., Methods: Of the 2005 patients with smear-positive bacterial ulcers screened, 280 patients were enrolled. Descriptive statistics were used to summarize and characterize the data., Results: Eligible patients in India had baseline factors associated with agricultural work (N = 132; 47%) and manual labor (N = 54; 19%), whereas patients in the United States were associated with contact lens wear (N = 11; 69%) (P <0.001). Nearly, 10% of patients with unilateral infectious keratitis are at risk of bilateral blindness because of preexisting visual disability in their other eye and thus ineligible for inclusion. India had higher rates of exclusionary factors for blindness in the other eye such as cataract (N = 48; 27%) and glaucoma (N = 24; 13) compared with the United States (N = 0; 0%) (P <0.001)., Conclusions: While corneal ulceration is an important cause of disability in technologically advanced countries, it occurs more frequently in low and middle-income countries, and the implications on these populations should be considered. These baseline factors can be evaluated to address such health care disparities., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Topic: To provide an overview on the incidence of Acanthamoeba keratitis (AK)., Clinical Relevance: Although being a sight-threatening cause of infectious keratitis, a comprehensive assessment of the incidence of AK is lacking., Methods: Incidence of AK was computed as the number of eyes with AK per health care center, per year (annualized center incidence [ACI]). Two meta-analytical ratios also were calculated: (1) the ratio of eyes with AK to the count of eyes with nonviral microbial keratitis (MK) and (2) the ratio of eyes with AK to the overall population (i.e., the total number of people in a nation or region, as indicated by the authors in each study). Center was defined as the health care facility where the study took place. Actual and projected estimates of the number of eyes with AK in years were calculated multiplying the ratio of eyes with AK to the total population and the corresponding population estimates, sourced from the United Nations Population Prospects., Results: Overall, 105 articles were included, published between 1987 and 2022. The total number of eyes identified was 91 951, with 5660 eyes affected by AK and 86 291 eyes affected by nonviral MK. The median ACI was 1.9 eyes with AK per health care center per year (95% confidence interval [CI], 1.5-2.6 eyes), with no statistically significant differences among continents. The ratio of eyes with AK to the total number of eyes with MK was 1.52% (95% CI, 1.03%-2.22%), whereas the ratio of eyes with AK in relationship to the entire population was estimated at 2.34 eyes per 1 000 000 people (95% CI, 0.98-5.55 per 1 000 000 people). The projected increase in the numbers of eyes with AK indicated an increase of 18.5% (n = 15 355 eyes with AK) in 2053 and 25.5% (n = 16 253 eyes with AK) in 2073, compared with the baseline of 2023 (n = 12 953 eyes with AK)., Discussion: Acanthamoeba keratitis emerged as a relatively low-incident disorder, and no significant differences in terms of its incidence were found among different continents., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: We sought to introduce the materials, design, and biocompatibility of a flexible and suturable artificial corneal device., Methods: Single-piece, fully synthetic, optic-skirt design devices were made from compact perfluoroalkoxy alkane. The skirt and the optic wall surfaces were lined with a porous tissue ingrowth material using expanded polytetrafluoroethylene. Full-thickness macroapertures around the skirt perimeter were placed to facilitate nutrition of the recipient cornea. Material properties including the skirt's modulus of elasticity and bending stiffness, optic light transmission, wetting behavior, topical drug penetrance, and degradation profile were evaluated., Results: The final prototype suitable for human use has a transparent optic with a diameter of 4.60 mm anteriorly, 4.28 mm posteriorly, and a skirt outer diameter of 6.8 mm. The biomechanical and optical properties of the device closely align with the native human cornea with an average normalized device skirt-bending stiffness of 4.7 kPa·mm4 and light transmission in the visible spectrum ranging between 92% and 96%. No optical damage was seen in the 36 devices tested in fouling experiments. No significant difference was observed in topical drug penetrance into the anterior chamber of the device implanted eye compared with the naïve rabbit eye., Conclusions: The flexibility and biocompatibility of our artificial cornea device may offer enhanced tissue integration and decreased inflammation, leading to improved retention compared with rigid keratoprosthesis designs., Translational Relevance: We have developed a fully synthetic, flexible, suturable, optic-skirt design prototype artificial cornea that is ready to be tested in early human feasibility studies.

Importance: Evaluation of the microbiological diagnostic profile of multidrug-resistant Pseudomonas aeruginosa keratitis and potential management with rose bengal-photodynamic antimicrobial therapy (RB-PDAT) is important., Objective: To document the disease progression of carbapenemase-resistant P aeruginosa keratitis after an artificial tear contamination outbreak., Design, Setting, and Participants: This retrospective observation case series included 9 patients 40 years or older who presented at Bascom Palmer Eye Institute and had positive test results for multidrug-resistant P aeruginosa keratitis between January 1, 2022, and October 31, 2023., Main Outcomes and Measures: Evaluation of type III secretion phenotype, carbapenemase-resistance genes blaGES and blaVIM susceptibility to antibiotics, and in vitro and in vivo outcomes of RB-PDAT against multidrug-resistant P aeruginosa keratitis., Results: Among the 9 patients included in the analysis (5 women and 4 men; mean [SD] age, 73.4 [14.0] years), all samples tested positive for exoU and carbapenemase-resistant blaVIM and blaGES genes. Additionally, isolates were resistant to carbapenems as indicated by minimum inhibitory concentration testing. In vitro efficacy of RB-PDAT indicated its potential application for treating recalcitrant cases. These cases highlight the rapid progression and challenging management of multidrug-resistant P aeruginosa. Two patients were treated with RB-PDAT as an adjuvant to antibiotic therapy and had improved visual outcomes., Conclusions and Relevance: This case series highlights the concerning progression in resistance and virulence of P aeruginosa and emphasizes the need to explore alternative therapies like RB-PDAT that have broad coverage and no known antibiotic resistance. The findings support further investigation into the potential effects of RB-PDAT for other multidrug-resistant microbes.

Purpose: The aim of this study was to facilitate deep learning systems in image annotations for diagnosing keratitis type by developing an automated algorithm to classify slit-lamp photographs (SLPs) based on illumination technique., Methods: SLPs were collected from patients with corneal ulcer at Kellogg Eye Center, Bascom Palmer Eye Institute, and Aravind Eye Care Systems. Illumination techniques were slit beam, diffuse white light, diffuse blue light with fluorescein, and sclerotic scatter (ScS). Images were manually labeled for illumination and randomly split into training, validation, and testing data sets (70%:15%:15%). Classification algorithms including MobileNetV2, ResNet50, LeNet, AlexNet, multilayer perceptron, and k-nearest neighborhood were trained to distinguish 4 type of illumination techniques. The algorithm performances on the test data set were evaluated with 95% confidence intervals (CIs) for accuracy, F1 score, and area under the receiver operator characteristics curve (AUC-ROC), overall and by class (one-vs-rest)., Results: A total of 12,132 images from 409 patients were analyzed, including 41.8% (n = 5069) slit-beam photographs, 21.2% (2571) diffuse white light, 19.5% (2364) diffuse blue light, and 17.5% (2128) ScS. MobileNetV2 achieved the highest overall F1 score of 97.95% (CI, 97.94%-97.97%), AUC-ROC of 99.83% (99.72%-99.9%), and accuracy of 98.98% (98.97%-98.98%). The F1 scores for slit beam, diffuse white light, diffuse blue light, and ScS were 97.82% (97.80%-97.84%), 96.62% (96.58%-96.66%), 99.88% (99.87%-99.89%), and 97.59% (97.55%-97.62%), respectively. Slit beam and ScS were the 2 most frequently misclassified illumination., Conclusions: MobileNetV2 accurately labeled illumination of SLPs using a large data set of corneal images. Effective, automatic classification of SLPs is key to integrating deep learning systems for clinical decision support into practice workflows., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The purpose is to assess the efficacy of rose bengal photodynamic antimicrobial therapy (PDAT) using different irradiation energy levels and photosensitizer concentrations for the inhibition of fungal keratitis isolates. Seven different fungi (Aspergillus fumigatus, Candida albicans, Curvularia lunata, Fusarium keratoplasticum, Fusarium solani, Paecilomyces variotii, and Pseudallescheria boydii) were isolated from patients with confirmed infectious keratitis. Experiments were performed in triplicate with suspensions of each fungus exposed to different PDAT parameters including a control, green light exposure of 5.4 J/cm 2 , 2.7 J/cm 2 (continuous and pulsed), and 1.8 J/cm 2 and rose bengal concentrations of 0.1%, 0.05%, and 0.01%. Plates were photographed 72 h after experimentation, and analysis was performed to assess fungal growth inhibition. PDAT using 5.4 J/cm 2 of irradiation and 0.1% rose bengal completely inhibited growth of five of the seven fungal species. Candida albicans and Fusarium keratoplasticum were the most susceptible organisms, with growth inhibited with the lowest fluence and minimum rose bengal concentration. Fusarium solani, Pseudallescheria boydii, and Paecilomyces variotii were inhibited by lower light exposures and photosensitizer concentrations. Aspergillus fumigatus and Curvularia lunata were not inhibited by any PDAT parameters tested. Continuous and pulsed irradiation using 2.7 J/cm 2 produced similar results. Rose bengal PDAT successfully inhibits the in vitro growth of five fungi known to cause infectious keratitis. Differences in growth inhibition of the various fungi to multiple PDAT parameters suggest that susceptibilities to PDAT are unique among fungal species. These findings support modifying PDAT parameters based on the infectious etiology., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Aim: Rose Bengal photodynamic antimicrobial therapy (RB-PDAT) has poor corneal penetration, limiting its efficacy against acanthamoeba keratitis (AK). Iontophoresis enhances corneal permeation of charged molecules, piquing interest in its effects on RB in ex vivo human corneas. Methods: Five donor whole globes each underwent iontophoresis with RB, soaking in RB, or were soaked in normal saline (controls). RB penetration and corneal thickness was assessed using confocal microscopy. Results: Iontophoresis increased RB penetration compared with soaking (177 ± 9.5 μm vs. 100 ± 5.7 μm, p  < 0.001), with no significant differences in corneal thickness between groups (460 ± 87 μm vs. 407 ± 69 μm, p  = 0.432). Conclusion: Iontophoresis significantly improves RB penetration and its use in PDAT could offer a novel therapy for acanthamoeba keratitis. Further studies are needed to validate clinical efficacy.

Purpose: To evaluate the incidence, clinical characteristics, microbiological profile, and therapeutic outcomes of corneal ulcers in individuals with chronic ocular graft-vs-host disease (coGVHD)., Design: Retrospective clinical cohort study., Methods: Review of individuals diagnosed with coGVHD following hematopoietic stem cell transplantation (HSCT) who were seen at the Bascom Palmer Eye Institute between May 2010 and November 2021. Baseline demographics, clinical characteristics, microbiological profile, risk factors for corneal ulceration, and treatment outcomes were collected. Etiology was deemed infectious in individuals with a positive culture or appropriate clinical scenario (presence of stromal infiltrate or hypopyon); otherwise, ulcers were presumed to be noninfectious. Treatment success was defined as reepithelialization with infiltrate resolution, and treatment failure as progression to corneal perforation or keratoplasty. Kaplan-Meier survival analysis estimated the incidence of ulceration. Cox regression analyses examined demographic and risk factors. Infectious and noninfectious ulcer groups were compared using 2-way independent t tests, 1-way analysis of variances, and χ 2 tests, as appropriate., Results: 173 individuals were included (53.7±14.4 years old; 59.0% male). Thirty-three individuals developed an ulcer 74.5±54.3 months after HSCT, with estimated 5- and 10-year incidences of 14% and 30%, respectively. Twenty-two (66.6%) ulcers were deemed infectious (15 microbiologically confirmed, 7 clinically) and 11 (33.3%) were deemed noninfectious. Risk factors for corneal ulceration included Black race (hazards ratio [HR] 2.89, 95% CI 1.30-6.42, P < .01), previous ocular surgery (HR 9.16, 95% CI 3.86-21.72, P < .01), eyelid margin abnormalities (HR 3.44, 95% CI 1.69-6.99, P < .01), and topical steroid use (HR 2.74, 95% CI 1.33-5.62, P < .01). Conversely, contact lens use reduced the risk of corneal ulceration (HR 0.29, 95% CI 0.13-0.66, P < .01). Infectious ulcers had a significantly higher frequency of treatment failure than noninfectious ulcers (57.1% vs 20.0%, P = .04)., Conclusion: Corneal ulceration is a potential complication of coGVHD, with several clinical features identified as risk factors. Infectious ulcers had worse outcomes than noninfectious ulcers., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: There is a need to understand physicians' diagnostic uncertainty in the initial management of microbial keratitis (MK). This study aimed to understand corneal specialists' diagnostic uncertainty by establishing risk thresholds for treatment of MK that could be used to inform a decision curve analysis for prediction modeling., Methods: A cross-sectional survey of corneal specialists with at least 2 years clinical experience was conducted. Clinicians provided the percentage risk at which they would always or never treat MK types (bacterial, fungal, herpetic, and amoebic) based on initial ulcer sizes and locations (<2 mm 2 central, <2 mm 2 peripheral, and >8 mm 2 central)., Results: Seventy-two of 99 ophthalmologists participated who were 50% female with an average of 14.7 (SD = 10.1) years of experience, 60% in academic practices, and 38% outside the United States. Clinicians reported they would "never" and "always" treat a <2 mm 2 central MK infection if the median risk was 0% and 20% for bacterial (interquartile range, IQR = 0-5 and 5-50), 4.5% and 27.5% for herpetic (IQR = 0-10 and 10-50), 5% and 50% for fungal (IQR = 0-10 and 20-75), and 5% and 50.5% for amoebic (IQR = 0-20 and 32-80), respectively. Mixed-effects models showed lower thresholds to treat larger and central infections ( P < 0.001, respectively), and thresholds to always treat differed between MK types for the United States ( P < 0.001) but not international clinicians., Conclusions: Risk thresholds to treat differed by practice locations and MK types, location, and size. Researchers can use these thresholds to understand when a clinician is uncertain and to create decision support tools to guide clinicians' treatment decisions., Competing Interests: Funding for this research was provided by the National Eye Institute (R01EY031033, M.A.W.) (P30 EY005722, S.F.) and a Research to Prevent Blindness Career Advancement Award (M.A.W.). The remaining authors have no funding or conflicts of interest to disclose. The funding support played no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To describe the long-term management of bilateral limbal stem cell deficiency secondary to a severe chemical burn., Methods: Descriptive case report., Importance: This case highlights the importance of early intervention in ocular chemical burns for the preservation of tissue integrity and avoidance of perforation. We also review the use of proper ocular surface reconstructive techniques to restore the function of the limbal area, as well as the immunomodulatory strategies and follow-up needed for these interventions.

Purpose: To report the biological stability and postoperative outcomes of a second-generation, single-piece, flexible synthetic cornea in a rabbit model., Methods: Device materials and design were amended to enhance biointegration. Optic skirt design devices were made from compact perfluoroalkoxy alkane with porous expanded polytetrafluoroethylene ingrowth surface overlying the skirt and optic wall. Sixteen devices were implanted into intrastromal pocket in rabbit eyes. Rabbits were randomly assigned to 6- and 12-month follow-up cohorts (n = 8 in each) postoperatively. Monthly examinations and optical coherence tomography assessed cornea-device integration, iridocorneal angle, optic nerve, and retina., Results: There were no intraoperative complications. All devices were in situ at exit, with clear optics. No retroprosthetic membrane, glaucoma, cataract formation, or retinal detachment was observed. Two rabbits in the 6-month group had mild, focal anterior lamella thinning without retraction adjacent to the optic near tight sutures. Three postoperative complications occurred in the 12-month group. One rabbit diagnosed with endophthalmitis was euthanized on day 228. Mild sterile focal retraction of anterior lamella occurred in two rabbits, which were terminated on days 225 and 315. Light microscopic examination of enucleated globes demonstrated fibroplasia with new collagen deposition into the porous scaffold without significant inflammation, encapsulation, or granuloma formation., Conclusions: Clinical evaluations, imaging, and histopathological findings indicate favorable outcomes of this synthetic corneal device in a rabbit model. Early feasibility studies in humans are being planned., Translational Relevance: Favorable 12-month results of the device in rabbits demonstrate vision-restoring potential in corneally blind individuals at high risk of failure with donor keratoplasty.

Purpose: The purpose of this study was to assess the role of combined surgical treatment of therapeutic penetrating keratoplasty and pars plana vitrectomy in the anatomical and functional outcome of infectious keratitis endophthalmitis., Methods: This study reviewed the medical records of 4 participating centers in the United States and Mexico. This study included patients with a clinical diagnosis of infectious keratitis endophthalmitis who had been treated with an early therapeutic penetrating keratoplasty and pars plana vitrectomy as the main treatment for endophthalmitis. From each medical record, the study retrieved demographic data, relevant medical and drug history, baseline clinical manifestation of endophthalmitis, best-corrected visual acuity, and the need for enucleation/evisceration for the control of the infection or any other reason through the follow-up., Results: The study included 48 patients (50.15 ± 20.6 years). The mean follow-up time was 13 ± 0.5 months. The mean best-corrected visual acuity at baseline was 2.1 ± 0.25 logarithm of the minimum angle of resolution. At month 12 was 2.09 ± 0.61 logarithm of the minimum angle of resolution ( P = 0.9). The overall prevalence of enucleation/evisceration was 8.3% (95% confidence interval: 2.32%-19.98%). The prevalence of a vision of no-light perception was 20.8% (95% confidence interval: 2.32%-19.98%)., Conclusions: Combined surgery for severe cases of infectious keratitis endophthalmitis eradicates the infection in most cases, while significantly improving the overall outcomes., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: This case describes the successful visual restoration of a patient with end-stage Stevens-Johnson syndrome (SJS) with a severely keratinized ocular surface., Methods: This study is a case report., Results: A 67-year-old man with SJS secondary to allopurinol sought visual rehabilitation options. His ocular surface was severely compromised from sequelae of chronic SJS, leaving him with light perception vision bilaterally. The left eye was completely keratinized with severe ankyloblepharon. The right eye had failed penetrating keratoplasty, limbal stem cell deficiency, and a keratinized ocular surface. The patient declined both a Boston type 2 keratoprosthesis and a modified osteo-odonto keratoprosthesis. Therefore, a staged approach was pursued with (1) systemic methotrexate to control ocular surface inflammation, (2) minor salivary gland transplant to increase ocular surface lubrication, (3) lid margin mucous membrane graft to reduce keratinization, and finally, (4) Boston type 1 keratoprosthesis for visual restoration. After minor salivary gland transplant and mucous membrane graft, the Schirmer score improved from 0 mm to 3 mm with improvement in ocular surface keratinization. This approach successfully restored the vision to 20/60, and the patient has retained the keratoprosthesis for over 2 years., Conclusions: Sight restoration options are limited in patients with end-stage SJS with a keratinized ocular surface, aqueous and mucin deficiency, corneal opacification, and limbal stem cell deficiency. This case demonstrates successful ocular surface rehabilitation and vision restoration in such a patient through a multifaceted approach that resulted in successful implantation and retention of a Boston type 1 keratoprosthesis., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Immunosuppression in aqueous-deficient dry eye disease (ADDE) is required not only to improve the symptoms and signs but also to prevent further progression of the disease and its sight-threatening sequelae. This immunomodulation can be achieved through topical and/or systemic medications, and the choice of one drug over the other is determined by the underlying systemic disease. These immunosuppressive agents require a minimum of 6-8 weeks to achieve their beneficial effect, and during this time, the patient is usually placed on topical corticosteroids. Antimetabolites such as methotrexate, azathioprine, and mycophenolate mofetil, along with calcineurin inhibitors, are commonly used as first-line medications. The latter have a pivotal role in immunomodulation since T cells contribute significantly to the pathogenesis of ocular surface inflammation in dry eye disease. Alkylating agents are largely limited to controlling acute exacerbations with pulse doses of cyclophosphamide. Biologic agents, such as rituximab, are particularly useful in patients with refractory disease. Each group of drugs has its own side-effect profiles and requires a stringent monitoring schedule that must be followed to prevent systemic morbidity. A customized combination of topical and systemic medications is usually required to achieve adequate control, and this review aims to help the clinician choose the most appropriate modality and monitoring regimen for a given case of ADDE., Competing Interests: None

Infectious scleritis is a potentially devastating condition that can result in severe vision loss. When traditional management fails, a subpalpebral antibiotic lavage system (SAL) can be considered to bathe the infected area with a high volume and concentration of antibiotics. Several reports show that this method can be curative for infectious scleritis, otherwise refractory to care. However, surgical approaches for this technique are either not well described, advocate for transecting the levator aponeurosis, or do not expose the entire width of the superior fornix, which can lead to postoperative ptosis. The authors describe a case where a novel approach was utilized, using a fenestrated angiocather in the superior lateral fornix, to maximize outcomes and minimize postoperative complications. In the setting of infectious scleritis refractory to traditional management, a SAL can be safely and effectively placed with the technique detailed in this report., Competing Interests: The authors report no conflict of interests., (Copyright © 2022 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Purpose: To evaluate the intermediate-term clinical outcomes of Rose Bengal Photodynamic Antimicrobial Therapy (RB-PDAT) for infectious keratitis; secondarily, to evaluate the surgical outcomes of individuals who underwent optical keratoplasty after RB-PDAT., Design: Retrospective cohort study., Method: A retrospective chart review was performed of 31 eyes from 30 consecutive individuals with infectious keratitis refractory to standard medical therapy who underwent RB-PDAT at the Bascom Palmer Eye Institute between January 2016 and July 2020. Data collected included demographics, risk factors for infectious keratitis, microbiological diagnosis, best spectacle-corrected visual acuity (BCVA), clinical outcomes after RB-PDAT, and complication rates post-keratoplasty. RB-PDAT was performed as described in previous studies. Graft survival was evaluated using Kaplan-Meier curves with log-ranks in individuals who underwent keratoplasty after RB-PDAT., Results: The mean age of the study population was 53 ± 18.0 years. In all, 70% were female; 53.3% self-identified as non-Hispanic White and 43.3% as Hispanic. Mean follow-up time was 28.0 ± 14.4 months. Risk factors included contact lens use (80.6%), history of infectious keratitis (19.3%), and ocular surface disease (16.1%). Cultures were positive for Acanthamoeba (51.6%), Fusarium (12.9%), and Pseudomonas (6.5%). Of the individuals with Acanthamoeba infection, 22.5% were treated with concomitant Miltefosine. Clinical resolution was achieved in 77.4% of patients on average 2.72 ± 1.85 months after RB-PDAT, with 22.5% requiring therapeutic penetrating keratoplasties and 54.8% subsequently requiring optical penetrating keratoplasties. At 2 years, the overall probability of graft survival was 78.7%, and the graft failure rate was 21.3%., Conclusion: RB-PDAT is a potential adjunct therapy for infectious keratitis that may reduce the need for a therapeutic penetrating keratoplasty. Patients who undergo keratoplasty after RB-PDAT may have a higher probability of graft survival at 1 year postoperatively., (Copyright © 2022 Elsevier Inc. All rights reserved.)

A healthy middle-aged man sustained extensive burns after a motor vehicle accident, including fourth-degree burns to the ocular adnexa. He had bilateral eyelid necrosis with complete tissue loss to the orbital rim. Progressive corneal thinning occurred bilaterally despite frequent lubrication, weekly amniotic membrane placement, and a Gunderson flap, ultimately requiring evisceration of his OS. In accordance with family wishes to perform all interventions for the OD, he underwent ocular surface reconstruction with levator palpebrae superioris (LPS) and inferior oblique (IO) muscle flaps, supplemented with an orbital fat transfer and bucket-handle muscle flap. These flaps were covered with porcine urinary bladder matrix and remained viable with complete globe coverage postoperatively. Although local eyelid flaps traditionally involve tissue supplied by branches of the external carotid artery, this case suggests that orbital-internal carotid artery based flaps utilizing the LPS and IO muscles may achieve ocular surface coverage after complete periocular and facial soft tissue loss., Competing Interests: The authors have no financial or conflicts of interest to disclose., (Copyright © 2022 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Purpose: The purpose of this study was to report the indications, ocular and systemic comorbidities, and surgical outcomes of corneal transplantation in patients older than 90 years., Methods: A retrospective review was conducted to identify individuals 90 years and older who underwent corneal transplantation surgery at the Bascom Palmer Eye Institute between January 2013 and October 2020. Outcomes included best-corrected visual acuity and graft survival over time. Paired t tests were used to compare visual acuity preoperatively versus postoperatively. Graft survival was evaluated with Kaplan-Meier curves., Results: Fifty-eight eyes of 52 consecutive individuals were included. The mean age of individuals was 92 ± 2 years; 26.9% were male; and 48.1% self-identified as non-Hispanic White and 38.5% as Hispanic. Postoperative follow-up was 14.7 ± 12.1 months. Of the 58 eyes, 44.8% (26/58) underwent penetrating keratoplasty, 46.6% (27/58) Descemet stripping automated endothelial keratoplasty, and 6.9% (4/58) keratoprosthesis. All surgeries were performed under monitored local anesthesia, without major complications. Surgical indications included pseudophakic bullous keratopathy (36.2%), glaucoma-associated corneal decompensation (27.6%), Fuchs endothelial dystrophy (25.9%), and perforated corneal ulceration (19.0%). The best-corrected visual acuity improved by 0.32 (95% confidence interval 0.14-0.50; P < 0.01) as early as 1 month postoperatively, and vision gains were sustained for at least 12 months. Graft survival probability at 12 months was 88%., Conclusions: Corneal transplantation is a safe and successful procedure in restoring the visual acuity for patients older than 90 years after careful preoperative evaluation. Further research is needed to evaluate the impact of corneal transplantation on quality of life in patients in the 10th decade of life., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: The aim of this study was to review the existing literature and investigate the role of microbiologic culture and histopathologic examination of corneal biopsies in the management of infectious keratitis., Recent Findings: Corneal biopsy continues to be a significantly useful tool in the diagnosis and tailored management of infectious keratitis. Several techniques can be employed for tissue collection, handling and processing to optimize diagnostic yield and maximize safety, including emerging femtosecond laser-assisted biopsy., Summary: Corneal opacities represent a significant cause of global blindness, and infectious keratitis is the most common cause. Organism identification in progressive infectious keratitis is essential for proper management. However, microbiological culture alone has a high rate of false-negative results. Records from the Bascom Palmer Eye Institute were retrospectively searched for patients between 1 January 2015, and 31 December 2019, who underwent corneal biopsy, therapeutic keratoplasty or endothelial graft removal for infectious keratitis and had specimens bisected and submitted for evaluation with both microbiologic culture and histopathologic examination. Detection of bacteria, fungus and mycobacteria was not statistically different between culture and histopathology. Microbiology and histopathology are complementary methods for the identification of causative microorganisms in corneal specimens with presumed infectious keratitis., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The impact of cataract surgery on low luminance visual acuity deficit (LLVAD) measurements was investigated by measuring the LLVAD before and after cataract surgery., Design: Prospective, longitudinal study., Participants: Patients undergoing cataract surgery., Methods: Photopic luminance (PL)-best-corrected visual acuity (BCVA) and low luminance (LL)-BCVA were obtained using the ETDRS chart. Low luminance visual acuity deficit scores were calculated by subtracting the LL-BCVA letter score from the PL-BCVA letter score. To demonstrate the reproducibility of these visual acuity measurements, we used data from drusen-only eyes previously published in the Complement Inhibition with Eculizumab for the Treatment of Nonexudative Age-Related Macular Degeneration (COMPLETE) study. The PL-BCVA, LL-BCVA, and LLVAD measurements obtained at an interval of 3 months in this cohort were used for comparison. In the current study, the impact of cataract surgery on LLVAD measurements was analyzed by comparing the PL-BCVA, LL-BCVA, and LLVAD measurements before and after cataract surgery., Main Outcome Measures: The reproducibility of the visual acuity measurements and the changes in LLVAD measurement after cataract surgery., Results: In the COMPLETE study, no clinically significant differences were found in the PL-BCVA, LL-BCVA, or LLVAD measurements between baseline and the 3-month follow-up visits with a change of -1.1 letters, -1.3 letters, and 0.1 letters, respectively ( P  = 0.02, P  = 0.11, and P  = 0.88, respectively). In the current study, significant increases were found in the PL-BCVA and LL-BCVA measurements, with a change of 7.3 letters and 10.2 letters after cataract surgery ( P < 0.001 for both), and a statistically significant decrease in LLVAD measurements was found, with a change of -3.0 letters after cataract surgery ( P  = 0.002)., Conclusions: Because of the variable effect of cataracts on LL-BCVA measurements and the significant change in LLVAD measurements after cataract surgery, investigators should be aware that cataract surgery during a trial will have an unpredictable impact on LLVAD measurements, and pseudophakic and phakic patients should be analyzed separately., (© 2022 Published by Elsevier Inc. on behalf of the American Academy of Ophthalmology.)