The Microbiome, Ocular Surface, and Corneal Disorders.

The ocular surface microbiome is an emerging field of study that seeks to understand how the community of microorganisms found on the ocular surface may help maintain homeostasis or can potentially lead to disease and dysbiosis. Initial questions include whether the organisms detected on the ocular surface inhabit that ecological niche and, if so, whether there exists a core microbiome found in most or all healthy eyes. Many questions have emerged around whether novel organisms and/or a redistribution of organisms play a role in disease pathogenesis, response to therapies, or convalescence. Although there is much enthusiasm about this topic, the ocular surface microbiome is a new field with many technical challenges. These challenges are discussed in this review as well as a need for standardization to adequately compare studies and advance the field. In addition, this review summarizes the current research on the microbiome of various ocular surface diseases and how these findings may impact treatments and clinical decision-making.

A Retrospective Analysis of Tear Film and Blink Parameters in Patients With Ocular Surface Disease.

OBJECTIVES: We had two objectives: (1) to investigate differences in tear film and blink parameters in patients with six ocular surface diseases (OSD): ocular graft versus host disease (oGVHD), Stevens-Johnson syndrome (SJS), lax eyelid syndrome, meibomian gland dysfunction (MGD), obstructive sleep apnea, and dry eye disease; and (2) to characterize the relationships between lipid layer thickness (LLT), meiboscore, Schirmer I test, and three blink parameters: partial blink rate (PBR), interblink interval (IBI), and interpalpebral fissure height (IPFH) in this group of patients. METHODS: This is a single-site retrospective analysis of 228 patients (456 eyes) with six different primary OSD at Loyola University Medical Center between January 2018 and July 2020. Objective parameters included: LLT, IBI, PBR, IPFH, Pult meiboscore, and Schirmer I score. Linear mixed effects models were used to analyze the relationships between these parameters. RESULTS: The meiboscore was highest in patients with SJS compared with the other five groups. There was significant variability in IPFH across different groups, with patients with oGVHD having the smallest height. An increase in IPFH was associated with increases in IBI, PBR, and Schirmer score. Patients with no partial blinks demonstrated a statistically significant higher IBI than patients who showed 1%-50% partial blinks. Finally, no statistically significant relationship was found between the following: (1) meiboscore and LLT, (2) OSDI and IPFH, (3) Schirmer score and IBI, or (4) LLT and IBI. CONCLUSIONS: There were fewer than anticipated differences in objective tear film and blink parameters between patients with six different OSD. A statistically significant association was found between IPFH and Schirmer score and IPFH and IBI, representing new findings in tear film research. Further investigation of the relationship between IPFH and IBI is needed.

Inflammation and oxidative stress induced by lipid peroxidation metabolite 4-hydroxynonenal in human corneal epithelial cells.

PURPOSE: Oxidative stress is widely known to be a major contributor in the pathogenesis of dry eye disease (DED). 4-Hydroxynonenal (4-HNE), a well-known byproduct frequently measured as an indicator of oxidative stress-induced lipid peroxidation, has been shown to be elevated in both human and murine corneal DED samples. This study aims to investigate if 4-HNE is responsible for the oxidative stress in human corneal epithelial cells (HCECs) and explores the underlying mechanism by which it confers its effects. METHODS: SV40-immortalized HCECs were cultured in minimum essential media (MEM) with 1% penicillin/streptomycin and 10% fetal bovine serum. HCECs were exposed to media with or without 4-HNE and cell culture supernatants were collected at 4 and 24 h. Cellular reactive oxygen species (ROS) measurement was performed using a 2',7'-dichlorofluorescein diacetate (DCFDA) assay kit according to the manufacturer's instructions. Protein levels of antioxidant enzymes copper/zinc superoxide dismutase 1 (SOD1) and NAD(P)H quinone dehydrogenase 1 (NQO1) were analyzed by Western blot. NF-κB activation and expression of IL-6 and IL-8 were measured using an NF-κB p65 Total SimpleStep ELISA Kit and Proteome Profiler Human Cytokine Array Kit. Cell viability was evaluated by LDH cytotoxicity assay. RESULTS: Treatment with 4-HNE decreased cell viability of HCECs. Band intensities corresponding to levels of ROS production showed a significant increase in ROS generation after treatment with 4-HNE. 4-HNE decreased SOD1 levels and upregulated NQO1 expression in HCECs. A significant increase in activation of NF-κB and production of pro-inflammatory cytokines IL-6 and IL-8 was observed after treatment with 4-HNE. Exposure to N-acetylcysteine (NAC), an antioxidant and ROS scavenger, antagonized the oxidative effects of 4-HNE on HCECs. CONCLUSION: 4-HNE induces oxidative stress in corneal epithelial cells by increasing levels of ROS generation and modifying the expression of antioxidant enzyme levels, decreasing cell viability of HCECs in vitro. This study demonstrates a potential pathway by which 4-HNE functions to confer its detrimental effects and provides a new therapeutic target for the treatment of DED.

Effects of activated omental cells on rat limbal corneal alkali injury.

Omental cells (OCs) are shown to help wound healing. The purpose of this study is to investigate if OCs improve cornea repair after alkali injury by subconjunctival injection of activated OCs in rats. Forty eight hours after limbal corneal alkali injury, fresh isolated OCs were injected subconjunctivally into the recipient rat's eye. Prior to the injury and at 0, 4 and 8 days after injury, the eyes were examined using slit lamp biomicroscopy. Corneal opacification and corneal neovascularization were graded in a masked fashion. The inflammatory response to the injury was evaluated by counting neutrophil cell numbers in the cornea under microscope. There was no significant difference in corneal opacification between the control and OCs treatment groups; however, the corneal neovascularization was significantly less in the eyes treated with OCs as compared to the controls. Also OCs treatment markedly decreased neutrophil infiltration after corneal-limbal alkali injury. Our results suggest that OCs may have a beneficial role in corneal healing after limbal corneal alkali injury by suppressing inflammatory cell infiltrates and corneal neovascularization.

The Impact of Donor History of Sleep Apnea on Corneal Tissue Evaluation Parameters.

PURPOSE: The goal of this study was to explore whether the donor history of sleep apnea affects corneal tissue evaluation parameters. METHODS: This was a retrospective study assessing the impact of donor history of sleep apnea in a dataset obtained from the Eversight Eye Bank. Comparative analysis and multivariate regression were used to assess differences in key parameters including endothelial cell density (ECD) and central corneal thickness. RESULTS: Data analyzed consisted of 50,170 tissues from 25,399 donors with no history of sleep apnea and 5473 tissues from 2774 donors with a history of sleep apnea. Tissue from donors with a history of sleep apnea showed lower ECD than those from donors with no history of sleep apnea (-51 cells/mm2, P < 0.001). Multivariate linear regression demonstrated that history of sleep apnea was a predictor of lower ECD by 13.72 cells/mm2 (P = 0.0264). Secondary analysis demonstrated that underweight and obese body mass indexes were significant predictors of increased ECD in donors with no history of sleep apnea (P < 0.0001, P = 0.025, respectively). Body mass index category was not a significant predictor of ECD in donors with a history of sleep apnea. In a smaller subset of 10,756 tissues, sleep apnea was not a significant predictor of central corneal thickness. CONCLUSIONS: This is the first study to demonstrate that a donor's history of sleep apnea is associated with a lower ECD in a large eye bank dataset. Future studies are needed to investigate whether history of sleep apnea affects posttransplantation outcomes.

Concurrent and face validity of a capsulorhexis simulation with respect to human patients.

A prototype version of the ImmersiveTouch® virtual reality simulator was applied to capsulorhexis, the creation of circular tear or "rhexis" in the lens capsule of the eye during cataract surgery. Virtual and live surgery scores by residents were compared. The same three metrics are used in each mode: circularity of the rhexis, duration of surgery (sec), and number of forceps grabs of the capsule per completed rhexis (fewer is better). The average simulator circularity score correlated closely with the average live score (P = 0.0002; N = 4), establishing "concurrent validity" for this metric. Individuals performed similarly to each other in both modes, as shown by the low standard deviations for average circularity (virtual 0.92 ± 0.04; live 0.88 ± 0.04). By contrast, the standard deviations are high for the other two metrics, capsulorhexis duration (virtual 96.91 ± 44.23 sec; live 94.42 ± 65.74 sec, N = 8) and number of forceps grabs (virtual 10.66 ± 4.81; live 10.31 ± 5.23, N = 8). Nevertheless, the simulator was able to demonstrate that the surgeons with wide variations in total duration and number of capsular grabs in 2 to 4 trials of simulated surgery also had similar variations in live surgery, so that the simulator retains some realism or "face validity."

A novel telemedicine technique for evaluation of ocular exam findings via smartphone images.

In this study, we compared the assessment of remote smartphone photographs to in-office exams in the diagnosis of two groups of external eye diseases, red-eye pathology and post-operative eyelid surgery complications. Participants were examined and received an in-office diagnosis by either a corneal or oculoplastic specialist. After viewing an educational video on smartphone photography, the patient's companion then took a series of standardized photographs. Two additional corresponding specialists then made a separate diagnosis via the interpretation of only smartphone images and the patient's history. 'Remote' and in-office diagnoses were compared using a kappa test for agreement. The remote and in-office diagnoses were in agreement for 27 of 28 eyes, representing a chance-corrected Kappa agreement rate of 93% (95% confidence interval: 79-99%). Among the 16 red eyes, the diagnoses were in agreement for 15 of 16 red eyes, representing a chance-corrected Kappa agreement rate of 92% (95% confidence interval: 77-99%). Among the 12 eyes with post-operative eyelid surgery complications, the diagnoses were in perfect agreement. Our results suggest that the diagnosis of 1) red-eye pathology and 2) post-operative eyelid surgery complications based on smartphone images may be comparable to in-office exams.

Acute and Chronic Management of Ocular Disease in Stevens Johnson Syndrome/Toxic Epidermal Necrolysis in the USA.

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.

Corneal perforation in ocular graft-versus-host disease.

PURPOSE: Corneal perforation is a rare, vision-threatening complication of ocular graft-versus-host disease (GVHD) and is not well understood. Our objective was to examine the clinical disease course and histopathologic correlation in patients who progressed to this outcome. METHODS: This study is a retrospective case series from four academic centers in the United States. All patients received a hematopoietic stem cell transplant (HSCT) prior to developing ocular GVHD. Variables of interest included patient demographics, time interval between HSCT and ocular events, visual acuity throughout clinical course, corticosteroid and infection prophylaxis regimens at time of corneal perforation, medical/surgical interventions, and histopathology. RESULTS: Fourteen eyes from 14 patients were analyzed. Most patients were male (86%) and Caucasian (86%), and average age at time of hematopoietic stem cell transplant was 47 years. The mean interval between hematopoietic stem cell transplant and diagnosis of ocular graft-versus-host disease was 9.5 months, and between hematopoietic stem cell transplant and corneal perforation was 37 months. Initial best-corrected visual acuity was 20/40 or better in 9 eyes, and all eyes had moderate or poor visual outcomes despite aggressive management, including corneal gluing in all patients followed by keratoplasty in 8 patients. The mean follow-up after perforation was 34 months (range 2-140 months). Oral prednisone was used prior to perforation in 11 patients (79%). On histopathology, representative specimens in the acute phase demonstrated ulcerative keratitis with perforation but minimal inflammatory cells and no microorganisms, consistent with sterile corneal "melt" in the setting of immunosuppression; and in the healed phase, filling in of the perforation site with fibrous scar. CONCLUSIONS: In these patients, an extended time interval was identified between the diagnosis of ocular graft-versus-host disease and corneal perforation. This represents a critical window to potentially prevent this devastating outcome. Further study is required to identify those patients at greatest risk as well as to optimize prevention strategies.

The ophthalmologist's role in the management of acute Stevens-Johnson syndrome and toxic epidermal necrolysis.

Stevens-Johnson syndrome (SJS) and its more severe variant, toxic epidermal necrolysis (TEN), are relatively rare but have high mortality rates. Survivors are frequently afflicted with severe blinding ocular surface diseases. Recent literature in the areas of ophthalmology and dermatology illustrate that the ophthalmologist's role should no longer be considered secondary in the acute management of SJS/TEN. Accurately differentiating SJS or TEN from erythema multiforme majus (EMM) at the onset of the disease is important, because the management approach to these disease entities differs. Systemic cyclosporine and intravenous immunoglobulin have shown some potential as treatments for SJS/TEN, but their efficacies remain controversial. Amniotic membrane transplantation and intravenous corticosteroid pulse therapy at the acute stage have shown promise for preventing late sight-threatening cicatricial complications. An improved staging system for the ocular surface involvement of acute SJS/TEN, as well as better understanding of the underlying destructive pathogenic mechanism, should further improve our ability to predict ocular involvement and develop new therapeutics to abort destructive processes at the acute stage.

Assessing the ocular surface microbiome in severe ocular surface diseases.

PURPOSE: There is growing evidence for a critical role of the microbiome in ocular health and disease. We performed a prospective, observational study to characterize the ocular surface microbiome (OSM) in four chronic ocular surface diseases (OSDs) and healthy controls. METHODS: Sterile swabs were used to collect samples from each eye of 39 patients (78 eyes). Sterile technique and multiple controls were used to assess contamination during DNA extraction, amplification and sequencing. Concurrent use of topical antibiotics, steroids, and bandage contact lenses (BCLs) was documented. RESULTS: Despite the low biomass of the ocular surface, 47/78 (60%) eyes sampled had positive sequencing reads. We observed that half of patients (8/17, 47%) had distinct microbiomes in each eye. Healthy controls had a Lactobacillus/Streptococcus mixture or significant Corynebacterium. Staphylococcus predominated in 4/7 (57%) patients with Stevens-Johnson Syndrome (SJS) in at least one eye, compared to 0/10 healthy controls. Interestingly, 8/11 (73%) eyes with SJS were using BCLs, including 4/5 (80%) eyes dominated by Staphylococcus. Lax eyelid syndrome (LES) and Dry Eye Disease (DED) patients had similar OSMs, with Corynebacterium being the most prevalent bacteria. Alpha diversity was higher in controls and ocular graft-vs-host (oGVHD) patients compared to the other OSDs. CONCLUSIONS: Only 50% of the 39 patients had similar microbiomes in each eye. A majority of healthy eyes had a Lactobacillus/Streptococcus mix or Corynebacterium microbiome. Staphylococcus predominated in SJS, Lactobacillus in oGVHD, and Corynebacterium in DED and LES. There may be an association between different OSDs and the microbiome.

Infectious interface keratitis (IIK) following lamellar keratoplasty: A literature review.

PURPOSE: The purpose of this study was to review the published incidence, etiology, clinical features and management of patients who developed infectious interface keratitis (IIK) following lamellar keratoplasty. DESIGN: This study is a systematic literature review. METHODS: We conducted a systematic review of published Chinese and English report through a PubMed search with the medical subject headings using the following terms: corneal transplantation, keratoplasty, anterior lamellar keratoplasty (ALK), deep anterior lamellar keratoplasty (DALK), deep lamellar endothelial keratoplasty (DLEK), Descemet membrane endothelial keratoplasty (DMEK), Descemet stripping endothelial keratoplasty (DSEK), Descemet stripping automated endothelial keratoplasty (DSAEK), infectious interface keratitis (IIK), fungal keratitis, and bacterial keratitis. Data collected included patient demographics, surgical technique, clinical signs, treatment, outcomes, and donor rim cultures. A review of the relevant literatures was also undertaken. RESULTS: From 2007 to Feb. 2018, we identified 62 cases of IIK following lamellar corneal surgery. The mean age was 26.95 ±â€¯8.80 years with a male/female ratio of 11:8 in DALK/ALK group and 69.65 ±â€¯8.00 years with a male/female ratio of 17:16 in DSAEK/DSEK/DMEK group (no gender information for 10 cases). Of the 62 cases, 46 cases (75.41%) were fungal, 9 cases (14.75%) were bacterial, 2 cases (3.28%) were Actinomyces species, 1 case (1.64%) was acanthamoeba, and 4 cases (6.56%) were indeterminant. The mean onset of symptoms was postoperative day (POD) 49.47 ±â€¯48.56 in DALK/ALK group, and 53 ±â€¯112.01 in EK group, and 62.44 ±â€¯50.07 for the bacterial keratitis, and 51.5 ±â€¯102.42 for fungal keratitis. The mean postoperative follow-up period was 10.10 ±â€¯9.36 months in DALK/ALK group and 12.37 ±â€¯12.28 months in DSAEK/DSEK/DMEK group. Of the total 62 cases, 1 case (1.61%) with a Klebsiella pneumoniae positive donor rim cultures was associated with the same pathogen in the IIK, and 16 cases (25.81%) of fungal positive donor rim cultures were associated with the same pathogen in the IIK. Clinical signs included conjunctival injection, interface opacity, stromal edema for bacterial keratitis, and dense white infiltrates at the interface with endothelial plaques in some cases of fungal keratitis. Medical treatment included topical and oral antimicrobial agents. Surgical interventions included therapeutic keratoplasty. In 15 cases (24.19%), medical management was successful. Of the remaining 47 cases, 8 (12.90%) were managed with a repeat lamellar keratoplasty (LK) and 39 (62.90%) were unresponsive to conservative medical treatment and underwent a therapeutic keratoplasty (TKP). Post infectious best corrected visual acuity (BCVA) was logMAR 0 in 7 eyes (11.29%), better than or equal to logMAR 0.4 in 20 eyes (32.26%), less than logMAR 0.4 in 22 eyes (35.48%) and logMAR 0.7 or worse in 13 eyes (20.97%). In the rim culture negative group(n = 19), the average BCVA was logMAR 0.59 ±â€¯0.68, with was logMAR 0.44 ±â€¯0.74 in rim culture positive group (n = 15). There were three recurrence cases were reported after DMEK during the postoperative follow-up period. CONCLUSIONS: Infectious interface keratitis (IIK) is an uncommon complication of lamellar keratoplasty, but it can result in a substantial loss of vision or permanent blindness. Although graft infection can occur at any time following surgery, it most commonly (87%) occurred during the first 3 months postoperatively (54/62 cases). The most commonly reported causative organism of IIK following lamellar keratoplasty was C. albicans. Positive rim culture results can provide more rapid and appropriate treatment directed to the identified organism. Therapeutic keratoplasty (TKP) was the most common surgical procedure for the management of IIK. Visual outcomes post TKP are fair with 32.26% (20/62) of patients obtaining LogMAR 0.4 or better.

A Multicenter Study Evaluating the Risk Factors and Outcomes of Repeat Descemet Stripping Endothelial Keratoplasty.

PURPOSE: Descemet stripping endothelial keratoplasty (DSEK), currently the most common procedure for managing corneal endothelial dysfunction, may be repeated following DSEK failure from a variety of causes. This multicenter study reports the risk factors and outcomes of repeat DSEK. METHODS: This was an institutional review board-approved multicenter retrospective chart review of patients who underwent repeat DSEK. Twelve surgeons from 5 Midwest academic centers and 3 private practice groups participated. The Eversight Eye Bank provided clinical indication and donor graft data. We also assessed the role of the learning curve by comparing cohorts from the first and second 5-year periods. RESULTS: A total of 121 eyes from 121 patients who underwent repeat DSEK were identified. The average age of the patients was 70 ± 12 years. The most common indication for repeat DSEK was late endothelial graft failure without rejection (58%, N = 63). Average preoperative and 12-month postoperative repeat DSEK corrected distance visual acuities were 20/694 and 20/89, respectively. Visual acuity outcomes, endothelial cell density, and cell loss did not significantly vary between the 2 cohorts. Initial graft rebubble rates for the first and second cohorts were 51% and 25%. The presence of glaucoma, prior glaucoma surgery, or a history of penetrating (full thickness) keratoplasty did not significantly affect visual outcomes. The median, mean, and range of intraocular pressures before repeat DSEK were 15.0, 15.7, and 6 to 37 mm Hg, respectively. Patients with higher intraocular pressures before repeat DSEK had improved postoperative corrected distance visual acuities. CONCLUSIONS: Repeating DSEK improves vision following failed or decompensated DSEK surgery. Higher preoperative repeat DSEK IOPs were associated with improved visual outcomes, and initial graft rebubble rates, which decreased over time, were likely due to surgeon experience.

Ophthalmic Complications Following Acoustic Neuroma Resection.

BACKGROUND: Past studies have shown high rates of ocular complications with the need for ophthalmic surgery following acoustic neuroma resection (ANR). OBJECTIVE: To determine the rates of ophthalmic complications, referrals, and surgery following ANR, and the factors associated with poor outcomes. METHODS: A retrospective study of ophthalmic outcomes in patients who underwent ANR was conducted, following institutional review board approval. Surgical approach, tumor size, tumor characteristics, completeness of resection, postoperative House-Brackmann grades, ocular complications, referrals to ophthalmology, and ophthalmic treatments were recorded. RESULTS: Between 2007 and 2012, 174 patients underwent ANR. There were 3 surgical groups: retrosigmoid (n = 97), translabyrinthine (n = 59), and combined retrosigmoid and translabyrinthine (n = 18). Median tumor size was 2.2 cm. Postoperatively, 30% of patients had facial nerve dysfunction (House-Brackmann ≥3), which recovered to 19% by 1 mo and 8.6% by 1 yr following ANR. Fifty-six (32.9%) patients experienced ocular complications postoperatively, with lagophthalmos, dry eye, and blurry vision as the most common complications. Thirty-six (67.9%) of the patients who required ophthalmic treatment were managed nonsurgically, with just 13 (7.6%) patients requiring referral to an ophthalmologist. In total, only 9 (5.3%) patients received an ophthalmic procedure. Patients with tumors >2 cm, those undergoing combined retrosigmoid and translabyrinthine resection, and those with severe facial nerve dysfunction which did not improve in the first month following surgery were more likely to have poor ophthalmic outcomes. CONCLUSION: We present lower rates of ophthalmic complications following ANR than previously reported. Improved surgical technique, better postoperative eye care, and facial nerve monitoring most likely accounted for the improved ocular outcomes.

A comparison of topical chlorhexidine, ciprofloxacin, and fortified tobramycin/cefazolin in rabbit models of Staphylococcus and Pseudomonas keratitis.

AIMS: Chlorhexidine was evaluated as a potential topical therapy for experimental bacterial keratitis. METHODS: Chlorhexidine (0.01%) was compared to ciprofloxacin (0.3%) and tobramycin (1.36%)/cefazolin (5%) both in vitro and in vivo for the treatment of Staphylococcus aureus and Pseudomonas aeruginosa infections. The minimum inhibitory concentration (MIC) was established for each organism for each antibiotic, using a standardized method. One thousand (1000) colony-forming units (CFU) of S. aureus or P. aeruginosa was intrastromally injected into rabbit cornea. A total of 92 corneas were infected and then treated topically with antibiotics. The control eyes were treated with artificial tears. The rabbits were later sacrificed, and the corneal buttons were harvested. RESULTS: The MIC for chlorhexidine was

Superior Limbic Keratoconjunctivitis-like Inflammation in Patients with Chronic Graft-Versus-Host Disease.

PURPOSE: Describe the presentation and management of superior limbic keratoconjunctivitis (SLK)-like inflammation and secondary limbal stem cell dysfunction in the setting of ocular chronic graft-versus-host disease (cGVHD). METHODS: Retrospective observational case series in a multicenter clinical practice. Participants were 13 patients (26 eyes) with ocular cGVHD and SLK-like inflammation presenting to the University of Illinois at Chicago and BostonSight® between January 1, 2009 and July 1, 2013. MAIN OUTCOME MEASURES: 1) Reversal or worsening of SLK, and 2) development of limbal stem cell dysfunction. RESULTS: All eyes showed evidence of SLK-like inflammation and superior limbal stem cell dysfunction manifested by conjunctival injection and superior conjunctival and corneal staining. In addition to aggressive lubrication, management strategies for SLK included topical steroids (20/26), punctal occlusion (18/26), topical cyclosporine (24/26), autologous serum tears (12/26), therapeutic soft contact lens (13/26 eyes) and scleral lenses (4/26 eyes). SLK and limbal stem cell dysfunction were reversed in 23/26 eyes. Three eyes of two patients with long-standing disease demonstrated frank limbal stem cell deficiency (LSCD) and corneal pannus, with one patient requiring multiple reconstructive surgical procedures. CONCLUSIONS: SLK-like inflammation is an under-recognized condition in patients with severe dry eyes secondary to ocular cGVHD. Untreated SLK can potentially lead to permanent LSCD over time. Early recognition and management of SLK in ocular cGVHD can improve vision, reverse signs, and may prevent these long-term consequences.

Acute and Chronic Ophthalmic Involvement in Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis - A Comprehensive Review and Guide to Therapy. II. Ophthalmic Disease.

Our purpose is to comprehensively review the state of the art with regard to Stevens- Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), with particular attention to improving the management of associated ocular surface complications. SJS and TEN are two ends of a spectrum of immune-mediated disease, characterized in the acute phase by a febrile illness followed by skin and mucous membrane necrosis and detachment. Part I of this review focused on the systemic aspects of SJS/TEN and was published in the January 2016 issue of this journal. The purpose of Part II is to summarize the ocular manifestations and their management through all phases of SJS/TEN, from acute to chronic. We hope this effort will assist ophthalmologists in their management of SJS/TEN, so that patients with this complex and debilitating disease receive the best possible care and experience the most optimal outcomes in their vision and quality of life.

Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis--A Comprehensive Review and Guide to Therapy. I. Systemic Disease.

The intent of this review is to comprehensively appraise the state of the art with regard to Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), with particular attention to the ocular surface complications and their management. SJS and TEN represent two ends of a spectrum of immune-mediated, dermatobullous disease, characterized in the acute phase by a febrile illness followed by skin and mucous membrane necrosis and detachment. The widespread keratinocyte death seen in SJS/TEN is rapid and irreversible, and even with early and aggressive intervention, morbidity is severe and mortality not uncommon. We have divided this review into two parts. Part I summarizes the epidemiology and immunopathogenesis of SJS/TEN and discusses systemic therapy and its possible benefits. We hope this review will help the ophthalmologist better understand the mechanisms of disease in SJS/TEN and enhance their care of patients with this complex and often debilitating disease. Part II (April 2016 issue) will focus on ophthalmic manifestations.

Amniotic membrane transplantation in the management of severe ocular surface disease: indications and outcomes.

Since 1995, with the availability of cryopreserved amniotic membrane (AM), the use of AM as a patch or graft for ocular surface reconstruction has become recognized as an important alternative for treatment of persistent epithelial defects and sterile ulceration that are refractory to conventional therapy. A major problem with evaluating the efficacy of AM transplantation is the lack of controlled clinical studies. Moreover, for some diseases there is no accepted "standard" therapy, and the incidence of the disease is too low to allow proper randomization. In this review, we have attempted to assess the indications and outcomes of AM transplantation based on 661 cases reported in the peer-reviewed literature. Successful outcome was defined as the healing of an epithelial defect (corneal or conjunctival) over a specified time period and the lack of induced motility disturbance.