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Purpose: To compare the effectiveness and efficiency of a glued (sutureless) technique for amniotic membrane transplantation (AMT) with a traditional sutured one in the setting of acute Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN)., Methods: This retrospective cohort study evaluated all patients diagnosed with SJS/TEN between 2008 and 2020 within our hospital network who received AMT in the acute phase according to our protocol and had at least one ophthalmic follow-up in the chronic phase. Primary outcomes included best-corrected visual acuity (BCVA) at the most recent visit, presence of a severe ocular complication (SOC) via predefined criteria, time to procedure and duration of procedure. Random effects model analysis was used to evaluate the impact of potential covariates on outcome measures., Results: A total of 23 patients (45 eyes) were included: 14 patients (27 eyes) in the AMT suture group and 9 patients (18 eyes) in the AMT glue group. There was no difference between the two groups in BCVA at the most recent visit (p=0.5112) or development of a SOC (p=1.000). The glue method was shorter in duration than the suture method (p<0.001). Random effects model additionally indicated that there was no difference in BCVA at most recent follow-up between patients who had received glued versus sutured AMT (p=0.1460)., Conclusions: Our glued technique for AMT is as effective as our sutured technique in stabilising the ocular surface and mitigating chronic ocular complications in SJS/TEN. The glued technique is also shorter in duration and performed more expediently than the sutured technique., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To evaluate ocular surface disease (OSD) in patients with childhood glaucoma (CG)., Methods: A multicenter, comparative, cross-sectional study of 41 eyes of 27 patients with CG and 42 eyes of 42 healthy age- and sex-matched controls was conducted between 2021 and 2022. Developmentally delayed children and those having a coexisting systemic illness that might affect the ocular surface were not enrolled. Data collected included glaucoma type, glaucoma medications and surgeries, anterior segment examination, symptom frequency and severity, and tear break-up time (TBUT). Dry eye disease (DED) symptoms were evaluated using an Arabic-language SPEED questionnaire., Results: The average number of glaucoma medications and surgeries among the 27 patients with CG was 1.17 and 1.4, respectively. TBUT was shorter in patients with CG compared with controls and even shorter when glaucoma medication usage was accounted for. Punctate epithelial erosions were more prevalent in patients with CG and of a higher grade. The severity of all DED parameters, and the prevalence of all DED parameters except for eye fatigue, were greater in patients with CG on the day of questionnaire intake. In addition, each additional glaucoma drop was associated with worse TBUT and ocular surface dryness. All analyses mentioned above were statistically significant (P < 0.05)., Conclusions: In this first study to comprehensively evaluate OSD in patients with CG, a significantly greater incidence of OSD signs and symptoms was found in patients with CG compared with a healthy population. Additional study by CG subtype is needed., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To develop an artificial intelligence (AI) model to diagnose Acanthamoeba keratitis (AK) based on in vivo confocal microscopy (IVCM) images extracted from the Heidelberg Retinal Tomograph 3 (HRT 3)., Methods: This retrospective cohort study utilized HRT 3 IVCM images from patients who had received a culture-confirmed diagnosis of AK between 2013 and 2021 at Massachusetts Eye and Ear. Two cornea specialists independently labeled the images as AK or nonspecific finding (NSF) in a blind manner. Deep learning tasks were then conducted through Python and TensorFlow. Distinguishing between AK and NSF was designed as the task and completed through a devised convolutional neural network., Results: A dataset of 3312 confocal images from 17 patients with a culture-confirmed diagnosis of AK was used in this study. The inter-rater agreement for identifying the presence or absence of AK in IVCM images was 84 %, corresponding to a total of 2782 images on which both observers agreed and which were included in the model. 1242 and 1265 images of AK and NSF, respectively, were utilized in the training and validation sets, and 173 and 102 images of AK and NSF, respectively, were utilized in the evaluation set. Our model had an accuracy, sensitivity, and specificity of 76 % each, and a precision of 78 %., Conclusions: We developed an HRT-based IVCM AI model for AK diagnosis utilizing culture-confirmed cases of AK. We achieved good accuracy in diagnosing AK and our model holds significant promise in the clinical application of AI in improving early AK diagnosis., Competing Interests: Declaration of competing interest The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

We report the case of an 80-year-old man with restrictive strabismus in lateral gaze following multiple oculoplastic procedures for idiopathic epiphora. Despite excellent initial response to nasal conjunctival recession with lysis of adhesions and a miminal recession of the medial rectus muscle, the patient suffered recurrence of diplopia associated with limitation of abduction due to aggressive, deep, subconjunctival scarring. Given the history of oral lichen planus (LP), the patient was diagnosed with ocular involvement of LP. He underwent a second conjunctival recession, this time accompanied by an intensive LP treatment regimen. Nine months after surgery, he remained diplopia free and orthophoric in primary gaze. Surgeons treating restrictive strabismus in patients with LP should consider implementing systemic and topical immunosuppressive treatment simultaneously with surgical management., (Copyright © 2024 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Vaccines are an effective tool to reduce the disease burden from infectious diseases on a population, infrastructural, and individual level. Before vaccines can be administered to populations at large, they must go through rigorous testing in the form of clinical trials. While vaccine trials can be used to assess the efficacy of interventions on a local populace as well as target local endemic diseases, most clinical trials are sponsored and conducted by companies in high-income countries (HICs). This can lead to vaccines that are not optimized for low- and middle-income countries (LMICs) and that often neglect to address diseases specific to the local population. This narrative review aims to explore the factors leading to discrepancies in the execution of and access to vaccine trials between HICs and LMICs, thus guiding future efforts in confronting them. This review was written using the literature sourced from the PubMed database and supplemented with articles from Google Scholar along with grey literature. Several themes are highlighted including poorly defined regulatory and ethical guidelines, staff shortages, lack of research infrastructure, and logistical barriers. We discuss how these challenges have affected vaccine development in various capacities through case examples of SARS-CoV-2, poliovirus, and malaria. Many challenges remain in equitable vaccine clinical trial development and implementation. Facilitating the implementation of locally sponsored vaccine clinical trials in LMICs may be one avenue to address these challenges. In doing so, LMICs can become active stakeholders in the health of their citizens by addressing endemic diseases, tailoring vaccine specifications based on local needs, and implementing wide-scale vaccine access and delivery.

Acanthamoeba Keratitis (AK) is a severe corneal infection caused by the Acanthamoeba species of protozoa, potentially leading to permanent vision loss. AK requires prompt diagnosis and treatment to mitigate vision impairment. Diagnosing AK is challenging due to overlapping symptoms with other corneal infections, and treatment is made complicated by the organism's dual forms and increasing virulence, and delayed diagnosis. In this review, new approaches in AK diagnostics and treatment within the last 5 years are discussed. The English-language literature on PubMed was reviewed using the search terms " Acanthamoeba keratitis" and "diagnosis" or "treatment" and focused on studies published between 2018 and 2023. Two hundred sixty-five publications were initially identified, of which eighty-seven met inclusion and exclusion criteria. This review highlights the findings of these studies. Notably, advances in PCR-based diagnostics may be clinically implemented in the near future, while antibody-based and machine-learning approaches hold promise for the future. Single-drug topical therapy (0.08% PHMB) may improve drug access and efficacy, while oral medication (i.e., miltefosine) may offer a treatment option for patients with recalcitrant disease.

Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) is a predominantly drug-induced disease, with a mortality rate of 15-20%, that engages the expertise of multiple disciplines: dermatology, allergy, immunology, clinical pharmacology, burn surgery, ophthalmology, urogynecology, and psychiatry. SJS/TEN has an incidence of 1-5/million persons per year in the United States, with even higher rates globally. One of the challenges of SJS/TEN has been developing the research infrastructure and coordination to answer questions capable of transforming clinical care and leading to improved patient outcomes. SJS/TEN 2021, the third research meeting of its kind, was held as a virtual meeting on August 28-29, 2021. The meeting brought together 428 international scientists, in addition to a community of 140 SJS/TEN survivors and family members. The goal of the meeting was to brainstorm strategies to support the continued growth of an international SJS/TEN research network, bridging science and the community. The community workshop section of the meeting focused on eight primary themes: mental health, eye care, SJS/TEN in children, non-drug induced SJS/TEN, long-term health complications, new advances in mechanisms and basic science, managing long-term scarring, considerations for skin of color, and COVID-19 vaccines. The meeting featured several important updates and identified areas of unmet research and clinical need that will be highlighted in this white paper., Competing Interests: KM was employed by Stevens-Johnson Syndrome Foundation. EJP reports grants from National Institutes of Health (R01HG010863, R01AI152183, U01AI154659) and from the National Health and Medical Research Council of Australia. She receives Royalties and consulting fees from UpToDate and has received consulting fees from Janssen, Verve, Biocryst, Regeneron, AstraZeneca and Novavax. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer OI declared a shared affiliation with the author AS to the handling editor at the time of review., (Copyright © 2023 Marks, Botta, Abe, Beachkofsky, Boothman, Carleton, Chung, Cibotti, Dodiuk-Gad, Grimstein, Hasegawa, Hoofnagle, Hung, Kaffenberger, Kroshinsky, Lehloenya, Martin-Pozo, Micheletti, Mockenhaupt, Nagao, Pakala, Palubinsky, Pasieka, Peter, Pirmohamed, Reyes, Saeed, Shupp, Sukasem, Syu, Ueta, Zhou, Chang, Becker, Bellon, Bonnet, Cavalleri, Chodosh, Dewan, Dominguez, Dong, Ezhkova, Fuchs, Goldman, Himed, Mallal, Markova, McCawley, Norton, Ostrov, Phan, Sanford, Schlundt, Schneider, Shear, Shinkai, Tkaczyk, Trubiano, Volpi, Bouchard, Divito and Phillips.)

Purpose of Review: Many systemic medications have been observed to cause ocular toxicity. A subset of these reactions is thought to involve immunomodulation or a hypersensitivity reaction. As new medications are developed, ocular adverse effects are becoming increasingly prevalent. Herein we review immune-mediated drug reactions affecting they eye with special attention to the hypersensitivity mechanisms leading to ocular toxicity., Recent Findings: Recent work has focused on mechanisms and risk of immune-mediated ocular adverse drug reactions including genetic susceptibility and loss of ocular immune privilege., Summary: Given the consequences of immune-mediated ocular adverse drug reactions, clinicians must be aware of these to facilitate early recognition and management. The prompt involvement of an ophthalmologist for diagnosis and management is often essential to preserve vision and avoid long-term morbidity., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

A large number of bacterial pathogens bind to host extracellular matrix (ECM) components. For example, many Gram-negative and Gram-positive pathogens express binding proteins for fibronectin (FN) on their cell surface. Mutagenesis studies of bacterial FN-binding proteins have demonstrated their importance in pathogenesis in preclinical animal models. However, means to draw on these findings to design therapeutic approaches that specifically target FN-bacteria interactions have not been successful because bacterial pathogens can elaborate several FN-binding proteins and also because FN is an essential protein and likely a nondruggable target. Here we report that select heparan compounds potently inhibit Streptococcus pneumoniae infection of injured corneas in mice. Using intact heparan sulfate (HS) and heparin (HP), heparinase-digested fragments of HS, HP oligosaccharides, and chemically or chemoenzymatically modified heparan compounds, we found that inhibition of S. pneumoniae corneal infection by heparan compounds is not mediated by simple charge effects but by a selective sulfate group. Removal of 2- O -sulfates significantly inhibited the ability of HP to inhibit S. pneumoniae corneal infection, whereas the addition of 2- O -sulfates to heparosan (H) significantly increased H's ability to inhibit bacterial corneal infection. Proximity ligation assays indicated that S. pneumoniae attaches directly to FN fibrils in the corneal epithelial ECM and that HS and HP specifically inhibit this binding interaction in a 2- O -sulfate-dependent manner. These data suggest that heparan compounds containing 2- O -sulfate groups protect against S. pneumoniae corneal infection by inhibiting bacterial attachment to FN fibrils in the subepithelial ECM of injured corneas. Moreover, 2- O -sulfated heparan compounds significantly inhibited corneal infection in immunocompromised hosts, by a clinical keratitis isolate of S. pneumoniae , and also when topically administered in a therapeutic manner. These findings suggest that the administration of nonanticoagulant 2- O -sulfated heparan compounds may represent a plausible approach to the treatment of S. pneumoniae keratitis., Competing Interests: CONFLICT OF INTEREST STATEMENT The authors declare no conflict of interest.

Objective: To describe the relationship between history of atopic disease on systemic and ocular manifestations of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN)., Methods: Retrospective chart review of patients with SJS/TEN patients. Those with and without prior atopic diagnosis were compared., Results: In total, 200 patients with SJS/TEN were identified. A total of 23 patients also had an atopic diagnosis. Four, 10, and 18 had atopic dermatitis, allergic rhinitis, and asthma respectively. Acute ocular severity was significantly worse in the atopic cohort. No significant differences in overall systemic severity of SJS or mortality were found between the atopic and non-atopic cohorts. Compared to our hospital system's general population, prevalence of an atopic diagnosis was significantly higher in those with SJS/TEN., Conclusion: Patients with a history of an atopic diagnosis appear to have more significant acute ocular involvement during their SJS/TEN hospitalization. Atopic conditions appear to occur more frequently in the SJS/TEN population compared to the general population.

Objective: To assess the cumulative incidence and risk factors for glaucoma development and progression within 1-2 years following corneal transplant surgery., Design: Retrospective cohort study., Methods: Patients undergoing penetrating keratoplasty (PK), deep anterior lamellar keratoplasty (DALK), Descemet stripping endothelial keratoplasty (DSEK), Descemet membrane endothelial keratoplasty (DMEK), Boston keratoprosthesis type I (KPro) implantation, or endothelial keratoplasty (DSEK or DMEK) under previous PK (EK under previous PK) at one academic institution with at least 1 year of follow-up were included. Primary outcome measures were cumulative incidence of glaucoma development and progression after corneal transplant, in patients without and with preoperative glaucoma, respectively. Risk factors for glaucoma development and progression were also assessed., Results: Four hundred and thirty-one eyes of 431 patients undergoing PK (113), DALK (17), DSEK (71), DMEK (168), KPro (35) and EK under previous PK (27) with a mean follow-up of 22.9 months were analyzed. The 1-year cumulative incidence for glaucoma development and progression was 28.0% and 17.8% in patients without and with preoperative glaucoma, respectively. In a Cox proportional hazards analysis, DSEK surgery, KPro implantation, average intraocular pressure (IOP) through follow-up and postoperative IOP spikes of ≥30 mmHg were each independently associated with glaucoma development or progression (p < 0.04 for all)., Conclusions: A significant proportion of patients developed glaucoma or exhibited glaucoma progression within 1 year after corneal transplantation. Patient selection for DSEK may partly explain the higher risk for glaucoma in these patients. Postoperative IOP spikes should be minimized and may indicate the need for co-management with a glaucoma specialist., (© 2022. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Mycoplasma pneumoniae induced rash and mucositis (MIRM) is a relatively newly identified clinical entity which is characterized by mucocutaneous manifestations in the setting of Mycoplasma infection. Though a clinically distinct disease, MIRM exists on a diagnostic continuum with entities including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, and the recently described reactive infectious mucocutaneous eruption (RIME). In this systematic review, we discuss published findings on the epidemiology, clinical manifestations, diagnosis, and management of MIRM, with an emphasis on ocular disease. Lastly, we discuss some of the most recent developments and challenges in characterizing MIRM with respect to the related diagnosis of RIME., Competing Interests: Declaration of competing interest The authors have no disclosures to make regarding financial or personal relationships with other people or organizations which could bias their work. They have no conflicts of interest to disclose., (Copyright © 2022. Published by Elsevier Inc.)

Corneal disease is a leading cause of blindness worldwide. For most blinding corneal conditions, keratoplasty is the only way of restoring sight. Unfortunately, access to corneal transplantation is widely variable, most notably due to the lack of suitable donor material. There exists significant disparity between the developed and developing world when it comes to access to cornea tissue, with supply often inversely proportional to burden of disease. The purpose of this review is to identify the current disparities in supply and demand of corneal donor tissue, understand how to access corneal tissue, and propose solutions that promote equitable care for patients with severe corneal disease.

Vaccines against coronavirus disease 2019 (COVID-19) have played an important global role in reducing morbidity and mortality from COVID-19 infection. While the benefits of vaccination greatly outweigh the risks, adverse events do occur. Non-ocular adverse effects of the vaccines have been well-documented, but descriptions of ophthalmic effects remain limited. This systematic review aims to provide an overview of reported cases of corneal adverse events after receiving vaccination against COVID-19 and to compile existing clinical data to bring attention to these phenomena. Our review discusses corneal graft rejection, including proposed mechanisms, herpetic keratitis, and other reported corneal complications. Ophthalmologists and primary care physicians should be aware of such possible associations.

Introduction: Mortality risk prediction is an important part of the clinical assessment in the Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) patient. The SCORTEN and ABCD-10 scoring systems have been used as predictive clinical tools for assessing this risk. However, some of the metrics required in calculating these scores, such as the total body surface area (TBSA) involvement, are difficult to calculate. In addition, TBSA involvement is calculated in a variety of ways and is observer dependent and subjective. The goal of this study was to develop an alternative method to predict mortality in patients with SJS/TEN., Methods: Data was split into training and test datasets and preprocessed. Models were trained using five-fold cross validation. Out of several possible candidates, a random forests model was evaluated as being the most robust in predictive power for this dataset. Upon feature selection, a final random forests model was developed which was used for comparison against SCORTEN., Results: The differences in both accuracy ( p = 0.324) and area under the receiver operating characteristic curve (AUROC) ( p = 0.318) between the final random forests model and the SCORTEN and ABCD-10 models were not statistically significant. As such, this alternative method performs similarly to SCORTEN while only requiring simple laboratory tests from the day of admission., Discussion: This new alternative can make the mortality prediction process more efficient, along with providing a seamless implementation of the patient laboratory tests directly into the model from existing electronic health record (EHR) systems. Once the model was developed, a web application was built to deploy the model which integrates with the Epic EHR system on the Fast Healthcare Interoperability Resources (FHIR) Application Programming Interface (API); this only requires the patient medical record number and a date of the lab tests as parameters. This model ultimately allows clinicians to calculate patient mortality risk with only a few clicks. Further studies are needed for validation of this tool., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shareef, Kwan, Lau, Tahboub and Saeed.)

Purpose: To report visual function and quality of life (VF/QOL) using the National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and the ocular surface disease index (OSDI) in patients in the chronic phase of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Methods: The NEI-VFQ-25 questionnaire was administered to 15 patients who received protocol-based care in the form of topical medications with or without amniotic membrane transplantation (AMT) for acute SJS/TEN. The scores obtained were compared with scores from a healthy population. The associations between the NEI-VFQ-25 and dry eye symptoms as measured by OSDI questionnaire were also studied. Results: Patients were surveyed at a mean of 4.47 ± 2.22 years after acute SJS/TEN. Eleven patients received AMT in the acute phase. The median best corrected visual acuity at the time of administration of the questionnaire was 20/20. The mean composite NEI-VFQ-25 score was 86.48 ± 12. Patients who received protocol-based treatment in the acute phase of SJS/TEN had comparable NEI-VFQ-25 scores with healthy subjects on all subscales except ocular pain ( p = 0.027) and mental health ( p = 0.014), which were significantly reduced. The NEI-VFQ-25 composite scores significantly correlated with OSDI (R = -0.75, p = 0.001). Conclusion: A protocol-based management strategy composed of early ophthalmic evaluation, grading based on severity, the use of topical corticosteroids and AMT in the acute phase of SJS/TEN in patients with ocular complications helped preserve the VF/QOL. This study highlights the impact of appropriate management of the ocular complications in the acute phase of SJS/TEN., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shanbhag, Tahboub, Chodosh and Saeed.)

Purpose: To evaluate the efficacy and safety of cenegermin 0.002% ophthalmic drops in the management of pediatric neurotrophic keratopathy (NK)., Methods: Retrospective chart review of children under the age of 18 years diagnosed with NK at Boston Children's Hospital/Massachusetts Eye and Ear Infirmary and treated with topical cenegermin 0.002% ophthalmic solution between June 2018 and June 2021 was performed. Data collection included etiology of NK, age at time of initiation of topical cenegermin, laterality, ethnicity, gender, history of previous ocular therapy, pre- and post-therapy best corrected visual acuity, pre- and post-therapy cornea examination, any adverse events from topical cenegermin, associated ocular conditions, and history of ocular surgeries., Results: The current study includes four eyes of four pediatric patients with a mean age of 4.5 ± 2.0 years at the time of initiation of topical cenegermin therapy. The mean time from NK diagnosis until start of topical cenegermin drops was 5.2 ± 4.3 months and mean follow-up time was 15 ± 9.6 months. In all four patients, marked improvement in epitheliopathy was demonstrated after completion of therapy. Best corrected visual acuity was measurable in 3 eyes of 3 patients, and it improved from a mean of 0.07 ± 0.01 to a mean of 0.29 ± 0.26 ( P  = 0.3). No adverse events related to cenegermin therapy were noted., Conclusion: Topical cenegermin was effective in improving corneal healing for pediatric NK.

Purpose: The aim of this study was to evaluate the clinical and topographic features of posterior polymorphous corneal dystrophy (PPCD) in children aged 15 years or younger with a long-term follow-up. Retrospective case series., Methods: A retrospective chart review of patients who were diagnosed with PPCD at Boston Children's Hospital from 1999 to 2020 was performed. Data collected included age at the time of diagnosis, slit lamp findings, cycloplegic refraction, best-corrected visual acuity, central corneal thickness, specular microscopy, and corneal topography findings whenever available., Results: Twenty-seven eyes of 19 patients were included (11 unilateral and 8 bilateral cases). Ten patients were girls (52.6%). Left eye was affected in 14 eyes. The mean age at the time of diagnosis was 8.5 ± 3.3 years, with a mean follow-up of 5.3 years. In unilateral cases, there was a statistically significant difference in the endothelial cell density (P = 0.01), coefficient variation (P = 0.03), and hexagonality (P = 0.01) between the affected and the contralateral unaffected eyes. The mean best-corrected visual acuity at initial presentation was 0.8 ± 0.2 compared with 0.9 ± 0.08 in unaffected eyes (P = 0.04). The mean astigmatism was higher in the affected eye (+1.7 diopters) compared with (+1.00) the unaffected eye (P = 0.07). At initial presentation, 7 of 27 eyes had amblyopia, which resolved, either partially or completely, in 5 eyes after treatment., Conclusions: PPCD can present early in children with astigmatism and anisometropic amblyopia. A careful slit lamp examination for children presenting with anisoastigmatism is necessary to diagnose PPCD. Contrary to adults, presentation is often unilateral. Such patients should be followed up regularly with cycloplegic retinoscopy to prevent and treat refractive amblyopia if present., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: The following authors have no financial disclosures (AME and HNS).

Competing Interests: The authors declare that they have no conflicts of interest to disclose.

Though corneal collagen cross-linking (CXL) is an increasingly available and effective treatment for keratoconus, few reports have considered its impact on pain-related physiology in depth. This comprehensive narrative review summarises mechanisms underlying pain in CXL and clinical care possibilities, with the goal of future improvement in management of CXL-related pain. Postoperative pain associated with CXL is largely due to primary afferent nerve injury and, to a smaller extent, inflammation. Chronification of pain after CXL has not been reported, even as long-term nerve damage without regeneration following standard CXL treatment is frequently observed. The lack of pain chronification may be due to the minimally invasive nature of the procedure, with its rapidly recovering superficial corneal wound, and to the positive anti-inflammatory changes of the tear film that have been described after CXL. Different CXL approaches have been developed, with the transepithelial epithelial-on technique (epi-on) associated with less postsurgical pain than the gold standard, epithelial-off technique (epi-off). After the first few days, however, the difference in pain scores and need for analgesics between epi-on and epi-off disappear. Patients experience relatively high-intensity pain the first few days post-CXL, and many strategies for acute pain control following CXL have been studied. Currently, no method of pain management is considered superior or universally accepted. Acute pain following CXL is a recognised and clinically significant side effect, but few CXL studies have systematically investigated postoperative pain and its management. This review aims to improve patient pain outcomes following this increasingly common procedure., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Diagnosis and treatment planning in ophthalmology heavily depend on clinical examination and advanced imaging modalities, which can be time-consuming and carry the risk of human error. Artificial intelligence (AI) and deep learning (DL) are being used in different fields of ophthalmology and in particular, when running diagnostics and predicting outcomes of anterior segment surgeries. This review will evaluate the recent developments in AI for diagnostics, surgical interventions, and prognosis of corneal diseases. It also provides a brief overview of the newer AI dependent modalities in corneal diseases.

Stevens Johnson syndrome and toxic epidermal necrolysis are on a spectrum of a severe, immune-mediated, mucocutaneous disease. Ocular involvement occurs in the vast majority of cases and severe involvement can lead to corneal blindness. Treatment in the acute phase is imperative in mitigating the severity of chronic disease. Advances in acute treatment such as amniotic membrane transplantation have shown to significantly reduce the severity of chronic disease. However, AMT is not a panacea and severe chronic ocular disease can and does still occur even with aggressive acute treatment. Management of chronic disease is equally critical as timely intervention can prevent worsening of disease and preserve vision. This mini-review describes the acute and chronic findings in SJS/TEN and discusses medical and surgical management strategies., Competing Interests: HS and JC are employed by Mass Eye and Ear which manufactures and distributes the Boston keratoprosthesis and is discussed in this article. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Metcalfe, Iqbal, Chodosh, Bouchard and Saeed.)

Purpose: The purpose of this study is to compare the severity of chronic ocular complications of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) induced by lamotrigine (LT) vs. trimethoprim-sulfamethoxazole (TS)., Methods: This retrospective cross-sectional study evaluated all SJS/TEN patients treated within our hospital network from 2008 to 2018. Inclusion criteria included patients with reactions identified as caused by either LT or TS, and patients with at least one ophthalmology follow up in the chronic phase (≥3 months from disease onset). Primary outcome measures included LogMAR best-corrected VA at most recent visit and the presence or absence of severe ocular complications (SOC). Secondary outcome measures included chronic ocular complication severity scores using a modified Sotozono scoring system., Results: Forty-eight eyes of 24 patients were included in the study. The mean duration of follow-up was 39.50 ± 35.62 vs. 48.17 ± 33.09 months, respectively (p = 0.482). The LT group had worse average VA at the most recent visit (LogMAR VA; 0.508 vs. 0.041, p < 0.0001) and had a higher prevalence of SOCs (66.7% vs. 8.3%, p = 0.0038). The LT group scored worse on Sotozono chronic complications scores for the cornea (1.875 vs. 0.5, p = 0.0018), eyelid margin (5.583 vs.3.083, p = 0.0010), and overall condition (8.500 vs. 4.833, p = 0.0015). Sub-analyses showed that a moderate or severe acute ocular severity score was a significant predictor of chronic outcomes., Conclusions: Compared to patients with TS-induced SJS/TEN, patients with LT-induced SJS/TEN developed worse chronic ocular complications on several parameters. Future prospective studies are warranted to provide additional insight into the drug type as a predictor of chronic ocular complications., (Copyright © 2021. Published by Elsevier Inc.)

Purpose: To characterize diphtheroid corneal infections in eyes in the chronic phase of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN)., Methods: Observational case series., Results: Four eyes of 3 patients were included in this review. Each eye presented with persistent corneal epithelial defect with corneal thinning in the chronic phase of SJS/TEN. None of the epithelial defects were associated with stromal infiltration. The corneas were cultured at the time of workup of persistent epithelial defect (3 eyes) or at time of tectonic penetrating keratoplasty after perforation (1 eye). Cultures yielded abundant growth of Corynebacterium spp., including Corynebacterium jeikeium (n = 2), Corynebacterium glucuronolyticum (n = 1), and a multidrug-resistant Corynebacterium striatum isolate (n = 1). The ocular surface was stabilized with surgical intervention (1 eye) or with introduction of fortified topical antibiotic based on laboratory identification and susceptibility testing of the isolated organisms (3 eyes). Numerous risk factors for microbial keratitis were present in all 4 eyes., Conclusions: In eyes with a persistent corneal epithelial defect in the chronic phase of SJS/TEN, even in the absence of an infiltrate, corneal culture should be undertaken. Recognition and treatment of Corynebacterium spp. as opportunistic pathogens may lead to favorable outcomes in cases of clinically sterile ulceration during the chronic phase of SJS/TEN., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To report a case of Ochrobactrum anthropi keratitis in an eye with a Boston type 1 keratoprosthesis., Methods: This is a case report and review of the literature., Results: A 78-year-old man with a history of implantation of a Boston type 1 keratoprosthesis in the left eye presented for a routine follow-up with no acute complaints. In the left eye, visual acuity was 20/60 and slit-lamp examination revealed a 1.5-mm inferotemporal corneal infiltrate adjacent to the optic stem. Corneal cultures grew abundant O. anthropi. After 7 weeks of topical antimicrobial therapy and placement of a temporary tarsorrhaphy, the keratitis resolved., Conclusions: Ochrobactrum anthropi is an organism associated with indwelling medical devices and can be pathogenic in eyes with implanted keratoprostheses., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To report a case series of patients with treatment-resistant Acanthamoeba keratitis (AK) using oral miltefosine, often as salvage therapy., Design: Descriptive, retrospective multicenter case series., Methods: We reviewed 15 patients with AK unresponsive to therapy who were subsequently given adjuvant systemic miltefosine between 2011 and 2017. The main outcome measures were resolution of infection, final visual acuity, tolerance of miltefosine, and clinical course of disease., Results: All patients were treated with biguanides and/or diamidines or azoles without resolution of disease before starting miltefosine. Eleven of 15 patients retained count fingers or better vision, and all were considered disease free at last follow-up. Eleven of 15 patients had worsening inflammation with miltefosine, with 10 of them improving with steroids. Six patients received multiple courses of miltefosine. Most tolerated oral miltefosine well, with mild gastrointestinal symptoms as the most common systemic side effect., Conclusions: Oral miltefosine is a generally well-tolerated treatment adjuvant in patients with refractory AK. The clinician should be prepared for a steroid-responsive inflammatory response frequently encountered during the treatment course., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the effect of systemic cyclosporine (CsA) on ocular disease in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) patients., Methods: In this retrospective, comparative cohort study at a single center, patients with a diagnosis of SJS/TEN and with at least 3 months of follow up were divided into two groups: those who received systemic CsA and those who did not receive systemic CsA. Best-corrected visual acuity (BCVA) and chronic ocular surface complications score (COCS) at final follow-up were compared between the two groups., Results: The median age and follow-up period of patients was 29 years (range, 1.5-71 years) and 16.8 months (range, 3.67-91.58 months), respectively. BCVA, COCS, meibomian gland dysfunction, limbal stem cell deficiency, and the need for mucous membrane grafting and scleral lenses were not significantly different between patients who received systemic CsA as compared to patients who did not receive systemic CsA., Conclusions: In this small cohort of patients with SJS/TEN, we could identify no association between the use of systemic CsA as a component of their initial therapy and chronic ocular complications., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To report the long-term outcomes of amniotic membrane (AM) use in the form of transplantation (AMT) and self-retained amniotic membrane (ProKera® device, PD) in acute Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN)., Methods: Electronic records of all patients with a diagnosis of SJS/TEN at Massachusetts Eye and Ear between January 2008 and January 2018 were reviewed. Patients who received AM in acute SJS/TEN were selected. Only patients with follow-up ≥ 3 months after discharge were included., Results: Data of 55 eyes of 29 patients were analyzed. All 55 eyes received the first AM at a median interval of 5 days (inter-quartile range (IQR): 3-7 days) after onset of skin rash. Fifty-six percent of eyes (31/55) received AMT while 44% (24/55) received PD. Forty percent of eyes (22/55) required a repeat AMT or PD. Median follow-up after initial AM was 2.5 years (IQR: 1.2-3.6 years). At last follow-up, the best-corrected visual acuity was ≥20/40 in 87% of eyes (48/55). The most common complications in the chronic phase were meibomian gland disease and dry eye, seen in 78% of eyes (43/55) and 58% of eyes (32/55) respectively., Conclusions: Long-term results show that early use of AM in the acute phase of SJS/TEN may be effective in mitigating severe vision loss after SJS/TEN. However, eyelid-related complications and dry eye remain a common problem even with the use of AM., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening conditions with high morbidity and mortality. Supportive care management of SJS/TEN is highly variable. A systematic review of the literature was performed by dermatologists, ophthalmologists, intensivists, and gynecologists with expertise in SJS/TEN to generate statements for supportive care guideline development. Members of the Society of Dermatology Hospitalists with expertise in SJS/TEN were invited to participate in a modified, online Delphi-consensus. Participants were administered 9-point Likert scale questionnaires regarding 135 statements. The RAND/UCLA Appropriateness Method was used to evaluate and select proposed statements for guideline inclusion; statements with median ratings of 6.5 to 9 and a disagreement index of ≤1 were included in the guideline. For the final round, the guidelines were appraised by all of the participants. Included are an evidence-based discussion and recommendations for hospital setting and care team, wound care, ocular care, oral care, urogenital care, pain management, infection surveillance, fluid and electrolyte management, nutrition and stress ulcer prophylaxis, airway management, and anticoagulation in adult patients with SJS/TEN., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are potentially fatal mucocutaneous diseases that can involve many organ systems. Manifestations of SJS/TEN outside of the skin, eyes, and oral mucosa are not well defined or well recognized, and, therefore, are often not addressed clinically. As supportive care improves and mortality from SJS/TEN decreases, chronic complications in affected organ systems are becoming more prevalent. Recognition of the manifestations of SJS/TEN in the acute phase is critical to optimal care. In this review, we review the organ systems that may be involved in SJS/TEN, provide an overview of their management, and propose a list of items that should be communicated to the patient and family upon discharge. The organ systems discussed include the pulmonary, gastrointestinal/hepatic, oral, otorhinolaryngologic, gynecologic, genitourinary, and renal systems. In addition, the significant psychosocial, nutritional, and pain consequences and management of SJS/TEN are discussed., Competing Interests: Conflict of interest statement: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2020.)

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are potentially life-threatening, immune-mediated adverse reactions characterized by widespread erythema, epidermal necrosis, and detachment of skin and mucosa. Efforts to grow and develop functional international collaborations and a multidisciplinary interactive network focusing on SJS/TEN as an uncommon but high burden disease will be necessary to improve efforts in prevention, early diagnosis and improved acute and long-term management. SJS/TEN 2019: From Science to Translation was a 1.5-day scientific program held April 26-27, 2019, in Vancouver, Canada. The meeting successfully engaged clinicians, researchers, and patients and conducted many productive discussions on research and patient care needs., (Crown Copyright © 2020. Published by Elsevier B.V. All rights reserved.)

Purpose: To describe the long-term effect of a treatment protocol for ocular involvement in acute Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), including focused ocular examination and pathology-appropriate use of lubrication, topical corticosteroids, topical antibiotics, and amniotic membrane transplantation (AMT)., Design: Retrospective, comparative case series., Methods: A total of 48 patients (96 eyes) were included in this study. Nine of 48 patients (18 eyes) had acute SJS/TEN from 2000 to 2007 and did not receive protocol care (Group I). Thirty-nine of 48 patients (78 eyes) had acute SJS/TEN from 2008 to 2017 and received protocol care (Group II). The main outcome measures were best-corrected visual acuity (BCVA) at final follow-up visit and incidence of complications in the chronic phase., Results: No eyes in Group I received AMT for SJS/TEN, compared to 87% of qualifying eyes in Group II (P < .0001) There was a significant difference in the proportion of eyes with BCVA ≥20/40 at last follow-up between Group I and Group II (33% vs 92%, P < .001). The proportion of eyes with vision-threatening complications in the chronic phase was significantly higher in Group I versus Group II (67% vs 17%, P = .002), with most complications occurring in the first 2 years after disease onset in both groups., Conclusions: A specific protocol for acute ocular care in SJS/TEN, including aggressive use of AMT, was highly successful in reducing corneal blindness and severe vision-threatening complications of the disorder., (Copyright © 2019. Published by Elsevier Inc.)

Amniotic membrane (AM) transplantation, when performed in the acute phase in Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) for patients with ocular complications, is known to reduce the morbidity of ocular complications in the chronic phase. In conditions such as SJS/TEN, AM needs to be secured to the ocular surface as well as the eyelids. Previously, techniques of securing a large sheet of AM with fibrin glue to the ocular surface and with sutures and bolsters to the eyelids have been described in the acute phase of SJS/TEN. These techniques often necessitate the use of an operating room in acutely ill patients. We describe a bedside technique that uses cyanoacrylate glue to secure the AM to the eyelids, as well as long-term outcomes in 4 patients with acute SJS/TEN. The combination of a custom symblepharon ring to secure AM over the entire ocular surface and cyanoacrylate glue to secure AM to the eyelid margins is quick, painless, does not require local or general anesthesia, and might prove useful in other conditions previously shown to benefit from AMT, such as ocular chemical injuries., (Copyright © 2019. Published by Elsevier Inc.)

Purpose: To report the outcomes of prosthetic replacement of the ocular surface ecosystem (PROSE) treatment in pediatric patients with chronic ocular surface disease associated with Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN)., Design: Retrospective, interventional case series., Methods: Patients aged 18 years or younger seen in consultation for PROSE treatment at a single center between January 1992 and December 2016 with a history of SJS/TEN were reviewed. Demographics, etiology of SJS/TEN, age at treatment milestones, best-corrected visual acuity (BCVA) at treatment milestones, and treatment failures were recorded. BCVA at the initial presentation visit was compared to BCVA at the time of PROSE device dispense and at the last recorded visit., Results: Twenty-seven female and 22 male patients were reviewed. Reported etiology was antibiotic (n = 19), antiepileptic (n = 9), antipyretic (n = 9), other (n = 3), and unknown (n = 9). The mean age was 6.4 years at disease onset and 9.3 years at time of initial presentation. The mean duration of follow-up was 5.45 years. The median BCVA at the initial presentation was 0.6 logMAR (20/80 Snellen), and was significantly improved to 0.18 logMAR (20/30 Snellen) at the time a PROSE device was dispensed (P < .0001). The median BCVA at the last recorded visit was significantly improved to 0.18 logMAR (20/30 Snellen, P = .0004). There were 15 patients who failed PROSE treatment (30.6%)., Conclusions: PROSE treatment is feasible in over two thirds of pediatric patients with chronic ocular surface disease related to SJS/TEN and results in significant improvement in vision that is durable over a period of many years., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To compare the outcomes of Boston keratoprosthesis type 1 implantation after failed keratoplasty in patients who are blind or sighted in the contralateral eye., Methods: Retrospective comparative case series of Boston keratoprosthesis type I recipients performed for failed keratoplasty, between January 1, 2008, and June 30, 2016, at a single center. Patients were divided based on the best-corrected visual acuity in the contralateral eye at the time of surgery: group I, ≤20/200, and Group II, >20/200. Preoperative diagnoses, postoperative visual acuity, device retention, and postoperative complications were compared., Results: Group I (37 eyes) and group II (36 eyes) had similar demographics, median preoperative best-corrected visual acuity (count fingers) in the operated eye, and median duration of postoperative follow-up (37.4 vs. 45.2 months, respectively). Keratoprosthesis retention after the first year postimplantation was significantly better in group I versus group II (P = 0.038). Sterile vitritis and sterile keratolysis occurred more frequently in group II compared with group I (P = 0.013 and P = 0.056, respectively). At final examination, visual outcomes were not significantly different between the 2 groups., Conclusions: Most patients with failed keratoplasty who were implanted with a Boston keratoprosthesis type I experienced improved vision, and visual acuity of the contralateral eye did not seem to influence the visual outcome of surgery. However, patients with good vision in the contralateral eye were more likely to experience complications, possibly because of reduced vigilance when the other eye has ambulatory vision.

Purpose: To review the published literature on outcomes of keratolimbal allograft (KLAL) for the surgical treatment of limbal stem cell deficiency (LSCD) and corneal blindness after severe corneal chemical injury., Methods: Literature searches were conducted in the following electronic databases: MEDLINE, EMBASE, Science Citation Index, CINAHL, LILACS and the Cochrane Library. Standard systematic review methodology was applied. The main outcome measure was the proportion of eyes with best-corrected visual acuity (BCVA) ≥20/200 at last follow-up. Other measures of allograft success were also collected., Results: We identified six reports in which KLAL outcomes in the eyes after chemical injury could be distinguished. There were no randomised controlled studies. The outcomes of KLAL in 36 eyes of 33 patients were analysed. One study with seven eyes did not specify KLAL follow-up specific to chemical injury. Median postoperative follow-up for the other 29 eyes in 26 patients was 42 months (range 6.2-114 months). In the same 29 eyes, 69% (20/29) had BCVA ≥20/200 at the last follow-up examination. Eighty-nine per cent of all eyes (32/36) underwent penetrating keratoplasty simultaneous or subsequent to KLAL., Conclusions: The number of studies where outcomes of KLAL in eyes with severe corneal chemical injury could be discerned was limited, and variability was observed in outcome reporting. The quality of evidence to support the use of KLAL in LSCD in severe chemical corneal burns was low. Standardisation and longer follow-up are needed to better define evidence-based best practice when contemplating surgical intervention for blindness after corneal chemical injury., Prospero Registration Number: CRD42017054733., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

A female neonate presented with a pedunculated left lateral epibulbar mass protruding through the eyelids that originated from the temporal cornea and superolateral bulbar and palpebral conjunctiva. She had a cleft in the ipsilateral central upper eyelid with horizontal kink of the tarsus lateral to the cleft and focal patches of alopecia on the scalp. Histopathology of the epibulbar mass revealed conjunctival epithelium with underlying connective tissue, cartilage, bone, adipose, and lacrimal gland consistent with epibulbar dermoid. Genetic testing of the surgical specimen was positive for a KRAS mutation at position 146. MRI showed subarachnoid asymmetry around the left temporal lobe and a C1-C2 enhancing lesion. These clinical and molecular findings suggest that this patient has a new clinical variant of oculoectodermal syndrome, a rare disorder associated with somatic KRAS gene mutations and characterized clinically by epibulbar dermoids, alopecia, aplasia cutis, brain anomalies, umbilical hernias, and congenital heart defects.

Purpose: To systematically review the published literature on outcomes of Boston keratoprosthesis type 1 for the treatment of limbal stem cell deficiency secondary to severe chemical corneal injury., Methods: Literature searches were conducted in MEDLINE (Ovid), Embase, Web of Science, and the Cochrane Central Register. The main outcome measures assessed were the proportion of eyes with best-corrected visual acuity (BCVA) ≥ 20/200 and the proportion retaining their original keratoprosthesis, both at the last recorded visit., Results: We identified 9 reports in which outcomes of Boston keratoprosthesis type I implantation after severe chemical injury could be determined, encompassing a total of 106 eyes of 100 patients. There were no randomized controlled studies. The median pre-operative BCVA was hand motion. Vision improved to ≥20/200 in 99/106 (93.4%) eyes after implantation. With a mean follow-up of 24.99 ± 14 months, 68/106 (64.1%) eyes retained BCVA ≥ 20/200 at the last examination. Therefore, 68/99 (68.7%) of those who improved to > 20/200 maintained at least this acuity. The originally implanted device was retained in 88/99 (88.9%) recipients for whom retention was reported. The mean time to failure was 22.36 ± 17.2 months. Glaucomatous optic neuropathy was the most common cause for BCVA <20/200 in eyes that retained the keratoprosthesis (18/27, 66.7%).., Conclusions: Implantation of a Boston keratoprosthesis type I in eyes with corneal blindness after severe chemical ocular injury leads to functional vision in the majority of recipients. Evidence was limited by variability in outcome reporting and an absence of controlled studies.., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a life-threatening, immunologically mediated, and usually drug-induced disease with a high burden to individuals, their families, and society with an annual incidence of 1 to 5 per 1,000,000. To effect significant reduction in short- and long-term morbidity and mortality, and advance clinical care and research, coordination of multiple medical, surgical, behavioral, and basic scientific disciplines is required. On March 2, 2017, an investigator-driven meeting was held immediately before the American Academy of Dermatology Annual meeting for the central purpose of assembling, for the first time in the United States, clinicians and scientists from multiple disciplines involved in SJS/TEN clinical care and basic science research. As a product of this meeting, this article summarizes the current state of knowledge and expert opinion related to SJS/TEN covering a broad spectrum of topics including epidemiology and pharmacogenomic networks; clinical management and complications; special populations such as pediatrics, the elderly, and pregnant women; regulatory issues and the electronic health record; new agents that cause SJS/TEN; pharmacogenomics and immunopathogenesis; and the patient perspective. Goals include the maintenance of a durable and productive multidisciplinary network that will significantly further scientific progress and translation into prevention, early diagnosis, and management of SJS/TEN., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. All rights reserved.)