New advances in medical management of dry eye: optimizing treatment strategies for enhanced relief.

PURPOSE: Dry eye disease (DED) is a prevalent ocular surface disease that is conventionally characterized by tear film hyperosmolarity and instability. This review presents a summarized classification of DED, followed by a comprehensive discussion of the most recent topical and systemic medications and clinical recommendations for selecting the most appropriate option for each patient. METHODS: An extensive literature search was conducted on electronic databases, such as PubMed, Scopus, and Web of Science, using keywords including "dry eye syndrome," "ocular surface disease," "medical management," "artificial tears," "topical immunomodulators," and "meibomian gland dysfunction." RESULTS: The underlying reasons for DED can range from insufficient aqueous tear production to increased tear evaporation. Recent literature has provided a more in-depth understanding of the pathophysiology of DED by examining the tear film's lipid, aqueous, and mucin layers. However, despite these advancements, medical management of patients with symptomatic DED has not fully reflected this modernized knowledge of its pathophysiology. CONCLUSION: To develop a rationalized strategy for treating DED, it is crucial to have updated knowledge of therapeutic options, their mechanisms of actions, and indications based on the DED type and underlying causes.

The Association Between Computerized Tomography Findings and Ocular Trauma Score in Open Globe Injury: The Prognostic Value of Imaging.

PURPOSE: The aim of this study was to evaluate the association between CT findings and Ocular Trauma Score (OTS) in open globe injury. METHODS: In 182 eyes with open globe injury, CT findings were categorized into 5 major types: scleral irregularity with decreased globe volume, dislocation of the crystalline lens, abnormal vitreous density, thickening of the chorioretinal layer, and intraocular foreign body/air. Association between different types and number of CT findings with OTS stages were evaluated through a multivariate analysis. RESULTS: Mean age of the patients was 38 ± 8.5 years. The most common CT findings were severe scleral irregularity or globe collapse (71.9%) and abnormal vitreous density (56%). The most common OTS stages were II (44.5%) and I (30.7%). In multivariate analysis, abnormal vitreous density (odds ratio [OR] = 2.11, p < 0.001), chorioretinal thickening (OR = 1.89, p < 0.001), and intraocular foreign body/air (OR = 1.58, p = 0.001) were associated with more advanced OTS stages (I or II). Mean OTS in eyes with 1, 2, and 3 CT findings were 66 (stage III), 47 (stage II), and 37 (stage I), respectively ( p value = 0.008). Presence of 2 (OR = 2.46, p < 0.001) and 3 (OR = 2.92, p < 0.001) CT findings were associated with more advanced OTS stages (I or II). CONCLUSIONS: The type and number of CT findings may help to predict the OTS stage and visual prognosis in eyes with open globe injury.

An Overview of Surgical Approaches for Lower Eyelid Blepharoplasty.

Age-related changes in the lower eyelid are noticed by patients as bags or circles under the eye, a tired look, and a flattened face. Lower eyelid blepharoplasty, in which the excess skin and/or orbital fat is excised and repositioned, is mainly performed for aesthetic reasons rather than the correction of functional abnormalities. Favorable outcomes for the combination of these approaches have been reported, but the most suitable surgical technique is still debated. This systematic narrative review deals with the indications, preoperative considerations, operative techniques, and complications of several different surgical approaches to lower eyelid blepharoplasty.

Improving the properties of fish skin collagen/silk fibroin dressing by chemical treatment for corneal wound healing.

Natural biomaterials are crucial in ocular tissue engineering because they allow cells to proliferate, differentiate, and stratify while maintaining the typical epithelial phenotype. In this study, membranes as dressings were formed from silk fibroin and collagen (Co) extracted from fish skin and then modified with carbodiimide chemical cross linker in different concentrations. The samples were evaluated by different analyses such as structural, physical (optical, swelling, denaturation temperature, degradation), mechanical, and biological (viability, cell adhesion, immunocytochemistry) assays. The results showed that all membranes have excellent transparency, especially with higher silk fibroin content. Increasing the cross linker concentration and the ratio of silk fibroin to Co increased the denaturation temperature and mechanical strength and, conversely, reduced the degradation rate and cell adhesion. The samples did not show a significant difference in toxicity with increasing cross linker and silk fibroin ratio. In general, samples with a low silk fibroin ratio combined with cross linker can provide desirable properties as a membrane for corneal wound healing.

A mutation in DOP1B identified as a probable cause for autosomal recessive Peters anomaly in a consanguineous family.

Purpose: Peters anomaly (PA) is a heterogeneous developmental disorder characterized by central corneal opacity and iridocorneal or corneolenticular adhesions. Although many causative genes have been identified, most screened patients do not have mutations in the known genes. We aimed to identify the genetic cause of Peters anomaly in a pedigree with three affected individuals. Methods: Slit-lamp biomicroscopy and ultrasound biomicroscopy were performed for definitive diagnosis. Exome sequencing was conducted on the DNA of all three patients. After identification of a candidate causative gene, expression of the gene was assessed with real-time PCR in various ocular tissues of three human embryos and three adults. Results: The patients were affected with isolated PA. The parents of the patients were related to one another. Inheritance of PA was autosomal recessive. After appropriate filtering of the exome data, a homozygous variation in DOP1B remained as the only candidate genetic cause of PA in the pedigree. The variant segregated with disease status in the pedigree and was absent among 800 control Iranians. The variant has been reported in various databases at frequencies of 0.006 or less only in the heterozygous state in some cohorts of African origin. The p.Val1660 amino acid affected by the mutation is completely conserved in mammals and birds during evolution. Expression of DOP1B was shown in all adult and embryonic lens, iris, cornea, sclera, and retina tissues that were tested. Conclusions: DOP1B that encodes DOP1 leucine zipper like protein B was identified as the putative PA-causing gene in pedigree PA-101. As DOP1B is positioned within the Down syndrome chromosomal region on chromosome 21, until now this gene has mostly been studied with respect to brain functions. However, members of the Dopey gene family have been shown to have roles in development in other organisms. Evidence of the expression of DOP1B in various PA-relevant eye tissues, which, to the best of our knowledge, is shown here for the first time, is to be noted. However, this finding does not necessarily implicate a specific role for DOP1B in eye development as the gene is expressed in many tissues. Ultimately, definitive assessment of the contribution of DOP1B to PA pathology awaits identification of mutations in the gene in unrelated patients with PA and functional studies.

Cell-based approaches towards treating age-related macular degeneration.

Age-related macular degeneration as one of the most common causes of worldwide vision loss needs a proper approach for treatment. Therein, cell therapy and regenerative medicine can hold a great promise to be an effective approach. Accordingly, some preclinical and clinical studies were conducted to search around the therapeutic influence of stem cells in Age-related macular degeneration models and subjects. Hereupon, the purpose of the current review is to discuss the mechanisms of age-related macular degeneration, appropriate animal models along with suitable dosage and route of stem cell administration for its treatment.

CHST6 mutations identified in Iranian MCD patients and CHST6 mutations reported worldwide identify targets for gene editing approaches including the CRISPR/Cas system.

PURPOSE: To identify CHST6 mutations in Iranians macular corneal dystrophy (MCD) patients and also to assess distribution of amino acids in the encoded protein that are affected by CHST6 mutations reported hitherto in various populations in order to predict gene regions that may be appropriate targets for gene editing approaches including the CRISPR/Cas system. The analysis will also reveal biologically and functionally important regions of the protein. METHODS: Mutation screening of CHST6 by sequencing was performed on 21 Iranian MCD-affected probands. Previously reported MCD causing CHST6 mutations were identified by searches in NCBI. RESULTS: Nineteen CHST6 mutations were found among the 21 Iranian patients, most of which were missense mutations and six of which were novel. Totally, 189 mutations among 375 MCD patients have been found worldwide, and 134 of these are missense mutations. The distribution of 88 amino acids affected by missense mutations along the length of the encoded protein was not random, and four regions of possible mutation clustering were noted. 25% of patients harbored mutations in a DNA region consisting of only 36 nucleotides. CONCLUSION: Similar to most populations, CHST6 mutations among Iranians are very heterogeneous as indicated by finding 19 different mutations among 21 MCD patients. Nevertheless, identification of four potential mutation clusters identifies regions that are most suitable for gene therapy targeting by the CRISPR/Cas approach. Additionally, the mutation clusters identify regions with potential structural and/or functional importance. Consistent with this, the amino acids in these regions are well conserved among various membrane-bound sulfotransferases.

Systematic review and meta-analysis investigating autograft versus allograft cultivated limbal epithelial transplantation in limbal stem cell deficiency.

PURPOSE: Currently, regenerative medicine has attracted much attention among researchers investigating new methods to treat ocular surface diseases. Based on this new concept, cultivated limbal epithelial transplantation (CLET), whether in the form of autograft or allograft, has emerged as a promising surgical procedure for treating limbal stem cell deficiency (LSCD). Given that there is no updated comparison between autograft and allograft CLETs, the present review and meta-analysis aims to compare and determine the efficacy of two different CLET techniques, autologous versus allogeneic, based on a literature review of relevant studies. METHODS: A comprehensive search of electronic databases, including PubMed, Web of Science, Cochrane Library, Embase and Scopus, for related articles was performed in March 2018 to obtain relevant articles and to conduct a meta-analysis investigating the success rate of ocular surface regeneration and two-line improvement in best-corrected visual acuity (BCVA) using autograft versus allograft transplantations. RESULTS: A total of 30 studies, including 1306 eyes from 1288 patients with LSCD, with a sample size ranging from 6 to 200 and follow-up period of 0.6-156 months, were reviewed. Of 1306 eyes, 982 (75.2%) underwent autograft and 324 (24.8%) received allografts from living or deceased donors. Meta-analysis revealed that there was no significant difference between autograft and allograft CLETs in terms of success rate and two-line BCVA improvement. The prospective studies showed a zero difference between the two groups; only two retrospective studies included in the analysis pulled the autografts up to 1.82 and 1.2 times more than allografts in terms of success rate and two-line BCVA improvement, respectively [pooled OR 1.82 (95% CI 0.80-4.11); pooled OR 1.2 (95% CI 0.54-2.65)]. There was no statistically significant evidence of bias in the meta-analysis in terms of success rates and two-line BCVA improvement. CONCLUSIONS: The present analysis revealed no significant differences in success rates or visual improvement between autograft and allograft surgical techniques.

Unrestricted somatic stem cells, as a novel feeder layer: Ex vivo culture of human limbal stem cells.

Ex vivo culture of limbal stem cells (LSCs) is a current promising approach for reconstruction of the ocular surface. In this context, 3T3 feeder layer cells (mouse embryo fibroblast) are generally utilized to maintain and expand LSCs. The aim of this study is to develop a novel culture method (animal-derived products free) to expand LSCs, using umbilical cord derived human unrestricted somatic stem cells (hUSSCs) instead of 3T3 cell with an emphasis on maintaining of the Stemness in LSCs. Using flow-cytometer, isolated hUSSCs were characterized for CD105, CD90, CD166, CD34, CD45, CD31 cell surface markers and their differentiation capability into adipogenic as well as osteogenic lineages were evaluated. In addition to colony-forming efficiency (CFE), epithelial lineage differentiation and karyotyping, LSC properties were evaluated for ABCG2, ΔNP63-α, CK19, CK3, and CK12 mRNA and protein expressions using quantitative RT-PCR (qRT-PCR) and immunocytochemistry, when these cells were co-cultured with hUSSCs (in comparison with 3T3 feeder layer). LSCs, co-cultured with hUSSCs, showed normal karyotype (46, XX), while they could efficiently form colony (86 ± 3) and display up-regulation of the genes associated with stemness and down-regulation of corneal epithelial differentiation genes. Consistent with 3T3 feeder cells, hUSSCs with spindle-shaped morphology and quick splitting up properties had ability to preserve the stem like-cell phenotype of LSCs. These findings were confirmed by qRT-PCR and flow-cytometer. Findings of present study suggest hUSSCs as a promising alternative method for 3T3 feeder layer cells, to preserve growth and stemness of LSCs ex vivo culture.

Accelerated versus conventional corneal collagen cross-linking in patients with keratoconus: an intrapatient comparative study.

PURPOSE: To compare the outcomes of the conventional and accelerated corneal collagen cross-linking (CXL) in patients with bilateral progressive keratoconus (KC). METHODS: Fifteen consecutive patients with bilateral progressive KC were enrolled. In each patient, the fellow eyes were randomly assigned to the conventional CXL (3 mW/cm2 for 30 min) or accelerated CXL (ACXL) (9 mW/cm2 for 10 min) groups. Manifest refraction; uncorrected and corrected distant visual acuity; maximum and mean keratometry; corneal hysteresis and corneal resistance factor; endothelial cell density and morphology; central corneal thickness; and wavefront aberrations were measured before and 12 months after the CXL. RESULTS: Manifest refraction spherical equivalent and refractive cylinder improved significantly only in conventional group. Uncorrected and corrected distant visual acuity did not change significantly in either group. Also there was no significant change in the maximum and mean keratometry after 12 months. There was significant decrease in central corneal thickness in both groups which was more prominent in conventional group. Endothelial cell density reduced only in the conventional group which was not statistically significant (P = 0.147). CH, CRF, and wavefront aberrations did not change significantly in either group. We did not observe any significant difference in the changes of the variables between the two groups. CONCLUSIONS: Accelerated CXL with 9 mW/cm2 irradiation for 10 min had similar refractive, visual, keratometric, and aberrometric results and less adverse effects on the corneal thickness and endothelial cells as compared with the conventional method after 12 months follow-up. However, randomized clinical trials with longer follow-ups and larger sample sizes are needed.

Keratoconus: exploring fundamentals and future perspectives - a comprehensive systematic review.

Background: New developments in artificial intelligence, particularly with promising results in early detection and management of keratoconus, have favorably altered the natural history of the disease over the last few decades. Features of artificial intelligence in different machine such as anterior segment optical coherence tomography, and femtosecond laser technique have improved safety, precision, effectiveness, and predictability of treatment modalities of keratoconus (from contact lenses to keratoplasty techniques). These options ingrained in artificial intelligence are already underway and allow ophthalmologist to approach disease in the most non-invasive way. Objectives: This study comprehensively describes all of the treatment modalities of keratoconus considering machine learning strategies. Design: A multidimensional comprehensive systematic narrative review. Data sources and methods: A comprehensive search was done in the five main electronic databases (PubMed, Scopus, Web of Science, Embase, and Cochrane), without language and time or type of study restrictions. Afterward, eligible articles were selected by screening the titles and abstracts based on main mesh keywords. For potentially eligible articles, the full text was also reviewed. Results: Artificial intelligence demonstrates promise in keratoconus diagnosis and clinical management, spanning early detection (especially in subclinical cases), preoperative screening, postoperative ectasia prediction after keratorefractive surgery, and guiding surgical decisions. The majority of studies employed a solitary machine learning algorithm, whereas minor studies assessed multiple algorithms that evaluated the association of various keratoconus staging and management strategies. Last but not least, AI has proven effective in guiding the implantation of intracorneal ring segments in keratoconus corneas and predicting surgical outcomes. Conclusion: The efficient and widespread clinical translation of machine learning models in keratoconus management is a crucial goal of potential future approaches to better visual performance in keratoconus patients. Trial registration: The article has been registered through PROSPERO, an international database of prospectively registered systematic reviews, with the ID: CRD42022319338.

Keratoconus: from fundamentals to future Artificial intelligence has changed how we treat the eye disease keratoconus in recent years. This study examines the many keratoconus therapies available, including surgery and contact lens wear, and how artificial intelligence can improve the safety and accuracy of these procedures. We combed through numerous papers to locate this data. To achieve the best outcomes, several parameters and methods should be evaluated. According to the study, some elements from eye scans are more useful than others. The idea behind using artificial intelligence is to help patients see better and treat keratoconus more effectively.

Anwar versus Melles deep anterior lamellar keratoplasty for keratoconus: a prospective randomized clinical trial.

PURPOSE: To compare the outcomes of 2 techniques (Anwar vs. Melles) of deep anterior lamellar keratoplasty (DALK) in patients with keratoconus. DESIGN: Randomized, double-blind clinical trial. PARTICIPANTS: Fifty-seven eyes of 57 patients 20 to 35 years of age were enrolled. METHODS: Patients with clinical diagnosis of keratoconus who were contact lens intolerant and whose corrected distance visual acuity (CDVA) was less than 20/80 were enrolled. Eligible eyes were allocated randomly into 2 groups: the Anwar technique (23 eyes) or the Melles technique (25 eyes). MAIN OUTCOME MEASURES: The primary outcome measure was CDVA. Secondary outcomes were spherical equivalent, contrast sensitivity, corneal aberrations, corneal biomechanical properties, endothelial cell count, and central corneal thickness. All outcomes were compared 15 months after surgery. RESULTS: The CDVA was 0.17 ± 0.09 logarithm of the minimum angle of resolution (logMAR) units and 0.18 ± 0.11 logMAR units in the Anwar and Melles groups, respectively (P = 0.803). Spherical equivalent was -1.82 ± 2.7 diopters (D) and -2.69 ± 3.94 D in the Anwar and Melles groups, respectively (P = 0.155). Overall, the difference in photopic and mesopic contrast sensitivity function between the 2 groups was statistically significant (P<0.05). There was no significant difference between 2 groups in total and higher-order aberrations up to the fifth order (P>0.05 for all parameters). Corneal hysteresis was not significantly different between the 2 groups (9.9 ± 0.8 vs. 9.9 ± 0.6; P = 0.606). The corneal resistance factor was 10.02 ± 0.8 and 10.13 ± 0.76 (P = 0.509). There was no significant difference in percentage of endothelial cell loss between the 2 groups (1 ± 2% vs. 1 ± 3% in the Anwar and Melles groups, respectively; P = 0.869). Mean central corneal thickness was 525.56 ± 47.87 µm versus 504.64 ± 54.20 µm in the Anwar and Melles groups, respectively (P = 0.155). CONCLUSIONS: The Anwar and Melles techniques of DALK have comparable visual acuity and refractive outcomes, aberrometric profiles, biomechanical properties, corneal thicknesses, and endothelial cell densities. However, patients who underwent the Anwar technique showed better contrast sensitivity.

Bacterial contamination of amniotic membrane in a tissue bank from Iran.

Human Amniotic Membrane (AM) transplantation can promote tissue healing and reduce inflammation, tissue scarring and neovascularization. Homa Peyvand Tamin (HPT) tissue bank has focused on manufacturing human cell and tissue based products including AM. The purpose of this study is to evaluate and identify bacterial contamination of AMs that is produced by HPT for several ophthalmic applications. From July 2006 to April 2011, 122 placentas from cesarean sections were retrieved by HPT after obtaining informed consent from the donors. Besides testing donor's blood sample for viral markers, microbiological evaluation was performed pre and post processing. During tissue processing, decontamination was performed by an antibiotic cocktail including; Gentamicin, Ceftriaxone and Cloxacillin. Of 271 cesarean section AM donors who were screened as potential donors, 122 were accepted for processing and assessed for microbiological contamination. Donors' age were between 21 and 41 years (Mean = 27.61 ± 0.24). More than 92% of mothers were in their first or second gravidity with full term pregnancies. The most prevalent organisms were Staphylococci species (72.53%). After processing, contamination rates markedly decreased by 84.62% (p value = 0.013). According to our results, most of bacterial contaminations were related to donation process and the contamination pattern suggests procurement team as a source. Therefore we recommend that regular training programs should be implemented by tissue banks for procurement staff. These programs should focus on improved donor screening and proper aseptic technique for tissue retrieval. We also suggest that tissue banks should periodically check the rate and types of tissue contaminations. These data help them to find system faults and to update processing methods.

The Ability of Antibody against Truncated Matrix Metalloproteinase 9 Peptide to Evaluate the Native Protein on Tear Drops of Dry Eye Disease Patients by a Point-of-Care Diagnostic System.

Purpose: To obtain a reactive and specific antibody against truncated matrix metalloproteinase 9 (MMP-9), that has reactivity toward the native protein. Precision, accuracy, specificity, and sensitivity were evaluated using a point-of-care test. Methods: An in silico study was used to confirm the anti peptide truncated MMP-9 is against native MMP-9. After an antibody titer assessment, purification, and characterization, the anti MMP-9 was assessed. The cut-off value was determined using the purified gelatinases of the supernatant HCT 116 cell line. The supernatant was purified by preparative native-polyacrylamide gel electrophoresis based on charge and size of the proteins. Furthermore, quality control (QC) of the results were performed following standard densitometry methods. Results: A truncated MMP-9 is the major epitope peptide that can trigger the immune system to scavenge for a specific and reactive antibody against the native MMP-9. The MMP-9 native protein is purified from the supernatant of the HCT 116 cell line and the commercially available, full-length MMP-9. The cut-off value was estimated at 30 µg/mL. QC results indicated that the specificity was 80%, sensitivity was 96.7%, accuracy was 91%, and precision was 91.66%. The area under curve was 0.827 (P < 0.001). The positive predictive value was 83%, and the negative predictive value was 96%. Conclusions: The antibody against the synthetic epitope peptide can detect the native MMP-9. Native MMP-9 is considered the main biomarker in an immunoassay POCT and is used to diagnose dry eye disease (DED). In accordance with QC results, MMP-9 point of care test can be utilized for screening patients suffering from DED.

Role of Blepharoexfoliation in Demodex Blepharitis: A Randomized Comparative Study.

PURPOSE: The purpose of this study was to evaluate the safety and efficacy of blepharoexfoliation in the treatment of Demodex blepharitis. METHODS: Patients with microscopically approved Demodex blepharitis were enrolled. Patients in the treatment group were treated once with in-office blepharoexfoliation (BlephEx LLC; Franklin, TN) using tea tree oil 2% shampoo, followed by eyelid scrubs with tea tree oil 2% shampoo twice a day for 8 weeks. Patients in the control group were treated with the same protocol, except for the in-office sham blepharoexfoliation procedure. As the main outcome measurement, the changes in the severity of symptoms [Ocular Surface Disease Index (OSDI) score] were compared. The changes in Demodex count and meibomian gland dysfunction (MGD) severity were compared as the secondary outcome measurements. RESULTS: Eighty-one patients (36 male and 45 female) were included. The mean age of the patients was 53.56 ± 8.13 years. The mean baseline OSDI score was 33.30 ± 11.80. The mean baseline Demodex count was 4.84 ± 1.49. The Demodex count at the baseline visit was moderately correlated with the baseline OSDI score (R = 0.526, P = 0.011) and baseline MGD severity ( P = 0.02). At the 8-week visit, the OSDI score was 22.62 ± 8.23 and 27.09 ± 9.11 in the blepharoexfoliation and control groups, respectively ( P = 0.016). At the 8-week visit, the Demodex count was 2.6 ± 1.08 and 3.03 ± 1.27 in the treatment and control groups, respectively ( P = 0.025). MGD improved in both groups ( P = 0.84). In the blepharoexfoliation group, the change in the OSDI score was moderately correlated with the baseline OSDI score (R = 0.611, P = 0.01). CONCLUSIONS: One session of blepharoexfoliation, followed by manual eyelid scrubs was more effective than eyelid scrubs alone in reducing patients' symptoms and Demodex count.

Association of 2 Lysyl Oxidase Gene Single Nucleotide Polymorphisms with Keratoconus: A Nationwide Registration Study.

Purpose: Keratoconus (KC) is the most common primary ectatic corneal disease, characterized by progressive thinning of the cornea, affecting its shape and structure and leading to visual loss. Lysyl oxidase is an important component of the extracellular matrix and contributes to the homeostasis of corneal stromal extracellular matrix via enzymatic reaction. This nationwide registration study aims to examine the association of KC with 2 known single nucleotide polymorphisms, rs2956540 and rs10519694, in a population of Iranian descent. Design: Case-control. Participants: One hundred seventy-eight subjects with KC and 180 clinically healthy subjects participated in the study. Methods: Genomic DNA was extracted from peripheral blood samples, and their genotypes were determined using tetra-primer amplification refractory mutation system-polymerase chain reaction. Main Outcome Measures: Allele frequency for rs2956540 and rs10519694. Results: Genotype frequency was significantly different between cases and controls for rs2956540 (P value = 0.019). The rs2956540 C allele carriers were significantly more frequent among KC cases than healthy controls (P valuechi-square = 0.015, P valueFisher exact = 0.017). There was a significant difference in genotype frequency between groups for rs10519694 (P value = 0.001). T allele carriers were significantly more frequent among KC patients (P valuechi-square = 0.002, P valueFisher exact = 0.001). Sex stratification revealed no significant differences in genotype frequency between males and females in cases and controls. Fitting the general linear model showed that rs10519694 could be considered a predictor for the development of KC (P value = 0.001); however, this was not observed for rs2956540 (P value = 0.323). Conclusions: rs2956540 and rs10519694 are associated with KC in a population of Iranian descent. rs10519694 could potentially be used for KC risk prediction.

Mustard Gas-Induced Ocular Surface Disorders: An Update on the Pathogenesis, Clinical Manifestations, and Management.

PURPOSE: Mustard gas (MG) is a potent blistering and alkylating agent that has been used for military and terrorism purposes. Ocular surface injuries are common after exposure to MG. This review provides an update on the pathophysiology, ocular surface complications, and treatment options for MG-related ocular injuries. METHODS: Required information was obtained by reviewing various databases such as Cochrane Library, Google Scholar, and PubMed until March 2022. Data were collected by using keywords: "mustard gas" OR "sulfur mustard" AND "eye" OR "cornea" OR "ocular complication" OR "keratitis" OR "keratopathy" OR "limbal stem cell deficiency" OR "dry eye." RESULTS: Chronic intracellular toxicity, inflammation, and ischemia have been shown to play an essential role in the pathogenesis of MG injury. Ocular surface injuries can have acute, chronic, and most distinctly a delayed-onset presentation leading to various degrees of limbal stem cell deficiency. To date, no treatment has been agreed on as the standard treatment for chronic/delayed-onset MG keratopathy. Based on the authors' experience, we propose a management algorithm for MG-related ocular surface injuries involving optimization of ocular health, anti-inflammatory therapy, and if needed surgical interventions. The management of chronic and delayed-onset presentation remains challenging. CONCLUSIONS: MG keratopathy is a unique form of chemical injury which can lead to a range of ocular surface pathologies. Long-term anti-inflammatory therapy even in patients with seemingly mild disease may potentially reduce the likelihood of the development of more severe delayed-onset disease.

Mini-Conjunctival Limbal Autograft (Mini-CLAU) Using Platelet-Rich Plasma Eye Drops (E-PRP): A Case Series.

PURPOSE: The purpose of this study was to introduce a new method of limbal stem cell transplantation using autologous platelet-rich plasma (E-PRP) eye drops for unilateral total limbal stem cell deficiency. METHODS: Patients with total unilateral limbal stem cell deficiency due to chemical burn underwent mini-conjunctival limbal autograft using autologous E-PRP drops. One small limbal block, measuring 2 × 2 mm, was harvested from the patients' contralateral healthy eye and transplanted to the diseased eye. All patients received E-PRP drops until achieving complete corneal epithelialization. Subsequent corneal transplantation was performed in eyes with significant stromal opacification. Corneal buttons obtained during corneal transplantation underwent immunohistochemistry for the evaluation of limbal stem cell markers (ABCG2 and P63). Visual acuity, epithelial healing, corneal clarity, and regression of corneal conjunctivalization/vascularization were evaluated after surgery. RESULTS: Ten patients with acid (n = 7) or alkali (n = 3) burn were included. The mean follow-up period was 21.7 ± 5.8 months (range, 12-32 months). Corneas were completely reepithelialized within 14.9 ± 3.5 days (range, 11-21 days). Corneal conjunctivalization/vascularization dramatically regressed 1 to 2 months after surgery in all cases, and corneal clarity considerably improved in 7 patients. In the 3 eyes with significant stromal opacification, subsequent optical penetrating keratoplasty was performed. The ocular surface was stable throughout the follow-up period in all eyes. BSCVA improved to 0.60 ± 0.0.32 and 0.46 ± 0.0.25 logMAR in eyes with and without corneal transplantation, respectively, at the final follow-up visit. ABCG2 and P63 markers were detected on corneal buttons after keratoplasty. CONCLUSIONS: Based on our clinical and laboratory findings, mini-conjunctival limbal autograft using E-PRP can be considered as a promising alternative to ocular surface reconstruction.

Genetic predisposition to ocular surface disorders and opportunities for gene-based therapies.

The ocular surface, comprised of the corneal and conjunctival epithelium, innervation system, immune components, and tear-film apparatus, plays a key role in ocular integrity as well as comfort and vision. Gene defects may result in congenital ocular or systemic disorders with prominent ocular surface involvement. Examples include epithelial corneal dystrophies, aniridia, ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome, xeroderma pigmentosum (XP), and hereditary sensory and autonomic neuropathy. In addition, genetic factors may interact with environmental risk factors in the development of several multifactorial ocular surface disorders (OSDs) such as autoimmune disorders, allergies, neoplasms, and dry eye disease. Advanced gene-based technologies have already been introduced in disease modelling and proof-of-concept gene therapies for monogenic OSDs. For instance, patient-derived induced pluripotent stem cells have been used for modelling aniridia-associated keratopathy (AAK), XP, and EEC syndrome. Moreover, CRISPR/Cas9 genome editing has been used for disease modelling and/or gene therapy for AAK and Meesmann's epithelial corneal dystrophy. A better understanding of the role of genetic factors in OSDs may be helpful in designing personalized disease models and treatment approaches. Gene-based approaches in monogenic OSDs and genetic predisposition to multifactorial OSDs such as immune-mediated disorders and neoplasms with known or possible genetic risk factors has been seldom reviewed. In this narrative review, we discuss the role of genetic factors in monogenic and multifactorial OSDs and potential opportunities for gene therapy.

Topical Erythropoietin for Treatment of Scleral Necrosis.

PURPOSE: To investigate the safety and efficacy of topical erythropoietin for the treatment of scleral necrosis. METHODS: This study enrolled eight consecutive patients with scleral necrosis due to previous ocular surgery, rheumatoid arthritis-associated necrotizing anterior scleritis, and thermal and chemical burns. Conventional treatments failed to heal avascular scleral lesions in all eyes. Patients were treated with topical erythropoietin (3000 IU/mL) four times a day. RESULTS: The mean patient age was 37.6 ± 15.5 years. The interval between the development of scleral necrosis and initiation of topical erythropoietin was 25.6 ± 12.0 days. The necrotic sclera completely healed within 31.9 ± 16.9 days in all patients. The avascular lesions did not recur, and there was no evidence of side effects during the study. CONCLUSION: Our results showed that topical erythropoietin could be safely used to manage scleral necrosis. Randomized clinical trials are needed to further explore the efficacy of this intervention in patients with avascular scleral lesions.