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Purpose: To design a novel efficacious scAAV-Gusb viral vector for treating Mucopolysaccharidosis Type VII (MPS VII) caused by a mutation in the β-Glu gene (Gusb allele)., Methods: β-Glu expression of single-stranded AAV-Gusb (ssAAV-Gusb) and self-complementary AAV (scAAV-Gusb) vectors are tested with cultured murine Gusb fibroblasts. The scAAV-Gusb vector was chosen in further studies to prolong the life span and treat corneal pathology of Gusb mice via intrahepatic injection of neonates and intrastromal injection in adults, respectively. Corneal pathology was studied using HRT2 in vivo confocal microscope and histochemistry in mice corneas., Results: Both ssAAV-Gusb and scAAV-Gusb vectors expressed murine β-Glu in cultured Gusb fibroblasts. The scAAV-Gusb vector had higher transduction efficiency than the ssAAV-Gusb vector. To prolong the life span of Gusb mice, neonates (3 days old) were administered with scAAV-Gusb virus via intrahepatic injection. The treatment improves the survival rate of Gusb mice, prolonging the median survival rate from 22.5 weeks (untreated) to 50 weeks (treated). Thereafter, we determined the efficacy of the scAAV-Gusb virus in ameliorating corneal cloudiness observed in aged Gusb mice. Both corneal cloudiness and stroma thickness decreased, and there was the presence of β-Glu enzyme activity in the Gusb corneas receiving scAAV-Gusb virus associated with morphology change of amoeboid stromal cells in untreated to characteristic dendritic keratocytes morphology after 4-12 weeks of scAAV-Gusb virus injection., Conclusion: Intrahepatic injection of scAAV-Gusb is efficacious in prolonging the life span of Gusb mice, and intrastromal injection can ameliorate corneal phenotypes. Both strategies can be adapted for treating other MPS., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier Inc.)

Corneal opacities are a major cause of vision loss worldwide. However, the current therapies are suboptimal to manage the corneal wound healing process. Therefore, there is an obvious need to develop new treatment strategies that are efficient in promoting wound healing in patients with severe corneal disorders. In this study, we investigated and compared the efficacy of adipose-derived mesenchymal stem cells (ADMSCs) and photobiomodulation (PBM) with polychromatic light in the NIR (600-1200 nm) alone and in combination, on corneal opacity, inflammatory response, and tissue architecture in a rat corneal opacity model created by mechanical injury. All animals were divided into four groups randomly following the injury: injury only (no treatment), ADMSCs treatment, PBM treatment and combined (ADMSCs+PBM) treatment (n = 12 eyes per group). At the 10th and 30th day following injury, corneal opacity formation, neovascularization, and corneal thickness were assessed. On the 30th day the harvested corneas were analyzed by transmission electron microscopy (TEM), histological evaluation, immunohistochemical (IHC) staining and real-time polymerase chain reaction (RT-PCR). On day 30, the corneal opacity score, neovascularization grade, and corneal thickness in all treatment groups were significantly lower in comparison with the untreated injured corneas. The TEM imaging and H&E staining together clearly revealed a significant enhancement in corneal regeneration with improved corneal microenvironment and reduced vascularization in the combined administration of PBM and ADMSCs compared to treatment of PBM and ADMSCs alone. In addition, the IHC staining, and RT-PCR analysis supported our hypothesis that combining ADMSCs therapy with PBM alleviated the inflammatory response, and significantly decreased scar formation compared to either ADMSCs or PBM alone during the corneal wound healing., Competing Interests: Declaration of competing interest The authors have declared that there is no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Granular corneal dystrophy type 2 (GCD2) is an autosomal dominant corneal stromal dystrophy that is caused by p.Arg124His mutation of transforming growth factor β induced (TGFBI) gene. It is characterized by well demarcated granular shaped opacities in central anterior stroma and as the disease progresses, extrusion of the deposits results in ocular pain due to corneal epithelial erosion. Also, diffuse corneal haze which appears late, causes decrease in visual acuity. The prevalence of GCD2 is high in East Asia including Korea. Homozygous patients show a severe phenotype from an early age, and the heterozygote phenotype varies among patients, depending on several types of compound heterozygous TGFBI mutations. In the initial stage, conservative treatments such as artificial tears, antibiotic eye drops, and bandage contact lenses are used to treat corneal erosion. Different surgical methods are used depending on the depth and extent of the stromal deposits. Phototherapeutic keratectomy removes anterior opacities and is advantageous in terms of its applicability and repeatability. For deeper lesions, deep anterior lamellar keratoplasty can be used as the endothelial layer is not always affected. Recurrence following these treatments are reported within a wide range of rates in different studies due to varying definition of recurrence and follow-up period. In patients who have undergone corneal laser vision-correction surgeries such as photorefractive keratectomy, LASEK, or LASIK including SMILE surgery, corneal opacity exacerbates rapidly with severe deterioration of visual acuity. Further investigations on new treatments of GCD2 are necessary.

Previously we found that inhibitor of differentiation 3 (Id3) gene, a transcriptional repressor, efficiently inhibits corneal keratocyte differentiation to myofibroblasts in vitro. This study evaluated the potential of adeno-associated virus 5 (AAV5)-mediated Id3 gene therapy to treat corneal scarring using an established rabbit in vivo disease model. Corneal scarring/fibrosis in rabbit eyes was induced by alkali trauma, and 24 h thereafter corneas were administered with either balanced salt solution AAV5-naked vector, or AAV5-Id3 vector (n = 6/group) via an optimized reported method. Therapeutic effects of AAV5-Id3 gene therapy on corneal pathology and ocular health were evaluated with clinical, histological, and molecular techniques. Localized AAV5-Id3 gene therapy significantly inhibited corneal fibrosis/haze clinically from 2.7 to 0.7 on the Fantes scale in live animals (AAV5-naked versus AAV5-Id3; p < 0.001). Furthermore, AAV5-Id3 treatment significantly reduced profibrotic gene mRNA levels: α-smooth muscle actin (α-SMA) (2.8-fold; p < 0.001), fibronectin (3.2-fold; p < 0.001), collagen I (0.8-fold; p < 0.001), and collagen III (1.4-fold; p < 0.001), as well as protein levels of α-SMA (23.8%; p < 0.001) and collagens (1.8-fold; p < 0.001). The anti-fibrotic activity of AAV5-Id3 is attributed to reduced myofibroblast formation by disrupting the binding of E-box proteins to the promoter of α-SMA, a transforming growth factor-β signaling downstream target gene. In conclusion, these results indicate that localized AAV5-Id3 delivery in stroma caused no clinically relevant ocular symptoms or corneal cellular toxicity in the rabbit eyes., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to characterize the wide phenotypic spectrum of Peters anomaly and to suggest a management algorithm based on disease phenotype., Methods: The charts of all children diagnosed with Peters anomaly between January 2000 and December 2013 were reviewed retrospectively. Anterior segment color photographs, anterior segment optical coherence tomography, and ultrasound biomicroscopy images were used to phenotype disease severity and to guide management. Disease severity was categorized to Peters anomaly type I and II according to lens involvement. Peters anomaly type I and II were further categorized from mild to severe disease according to the size and location of corneal opacity. Associated systemic findings were also documented., Results: Eighty eyes of 54 patients with Peters anomaly were identified, of which 28 (51.9%) had unilateral disease. Peters anomaly type I was present in 40 patients (57 eyes, 71.2%) and Peters anomaly type II in 14 patients (23 eyes, 28.8%). Nine eyes (11.3%) had phenotypic features that required observation only, 24 eyes (30%) were amenable to pupillary dilation, 43 eyes (53.8%) with large, dense central opacity required penetrating keratoplasty, and 4 eyes (5.0%) had no intervention because of very poor prognostic features. Associated systemic abnormalities occurred frequently in Peters anomaly (n = 20, 37.0%), with congenital heart defect being the most common morbidity (n = 10, 18.5%)., Conclusions: Peters anomaly presents with a variable phenotype ranging from minimal peripheral corneal opacity to extensive iris and lens adhesions with dense central corneal opacity detrimental to vision. Management can be standardized and guided by an algorithm based on phenotypic severity. Systemic abnormalities should be ruled out, regardless of the severity of Peters anomaly., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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

The eye has two converging lenses arranged in series: the cornea and the lens. They combine their powers. The image, which is naturally defocused ad infinitum, by crossing them successively, focuses on the retina to be seen clearly. Edema can cause the cornea to lose transparency while the clouding of lens leads to cataract. The loss of transparency of one or both lenses significantly affects the vision. Treating cataracts is a common practice. However, this can lead to the permanent loss of transparency of the cornea. A graft of the latter must then be carried out. How does this sometimes come about?, (© 2020 médecine/sciences – Inserm.)

Purpose: To compare the therapeutic effects of human derivatives in a mouse alkali burn model. Methods: The right eyes of mice were injured using NaOH. After alkali injury, one of the following agents was topically administered for 7 d: human amniotic membrane (hAM) suspension, human umbilical cord serum (hUCS), and human peripheral blood serum (hPBS), or saline. The epithelial defect areas on days 1, 2, and 3 degrees of opacity on days 2, 3, and 7, and corneal neovascularization (NV) areas on day 7 were evaluated. Histologic examination and mRNA expression levels of tumour necrosis factor (TNF)-α, interleukin (IL)-6, vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2, MMP-8, and MMP-9 were also evaluated on day 7. Results: The epithelial defect areas in the hUCS group were smaller than those in the control and hPBS groups on day 3 ( p  < .05, respectively). The epithelial defect areas in the hAM suspension group showed smaller than those in the control and hPBS groups on days 1 and 2 ( p  < .05, respectively). The degrees of opacity were lower in all treatment groups than that of the saline control group on day 7 ( p  < .05, respectively). Corneal NV areas were not different among groups on day 7 ( p =  0.20). The expression levels of TNF-α, IL-6, MMP-8, and MMP-9 mRNA and the infiltration of the inflammatory cells in all treatment groups were lesser than those in the control group on day 7 ( p<  .05, respectively). Conclusions: All treatments reduced inflammatory reactions and corneal opacity development. Corneal reepithelialization was faster in the hUCS group.

Purpose: Maintenance of a transparent corneal stroma is imperative for proper vision. The corneal stroma is composed of primarily collagen fibrils, small leucine-rich proteoglycans (SLRPs), as well as sparsely distributed cells called keratocytes. The lattice arrangement and spacing of the collagen fibrils that allows for transparency may be disrupted due to genetic mutations and injuries. The purpose of this study is to examine the therapeutic efficacy of human umbilical cord mesenchymal stem/stromal cells (UMSCs) in treating congenital and acquired corneal opacity associated with the loss of collagen V., Methods: Experimental mice, i.e., wild-type, Col5a1 f/f and Kera-Cre/Col5a1 f/f ( Col5a1 ∆st/∆st , collagen V null in the corneal stroma) mice in a C57BL/6J genetic background, were subjected to a lamellar keratectomy, and treated with or without UMSC (10 4 cells/cornea) transplantation via an intrastromal injection or a fibrin plug. In vivo Heidelberg retinal tomograph (HRT II) confocal microscopy, second harmonic generated (SHG) confocal microscopy, histology, and immunofluorescence microscopy were used to assess the corneal transparency of the regenerated corneas., Results: Col5a1 ∆st/∆st mice display a cloudy cornea phenotype that is ameliorated following intrastromal transplantation of UMSCs. Loss of collagen V in Col5a1 ∆st/∆st corneas augments the formation of cornea scarring following the keratectomy. UMSC transplantation with a fibrin plug improves the healing of injured corneas and regeneration of transparent corneas, as determined with in vivo HRT II confocal microscopy. Second harmonic confocal microscopy revealed the improved collagen fibril lamellar architecture in the UMSC-transplanted cornea in comparison to the control keratectomized corneas., Conclusions: UMSC transplantation was successful in recovering some corneal transparency in injured corneas of wild-type, Col5a1 f/f and Col5a1 ∆st/∆st mice. The production of collagen V by transplanted UMSCs may account for the regeneration of corneal transparency, as exemplified by better collagen fiber organization, as revealed with SHG signals.

Introduction: Corneal tattooing is a noninvasive technique which appears relatively well-tolerated in the medium term. We report the cases of 3 patients with a significant change in the color of their tattoos performed over 5 years previously., Patients and Methods: Three patients with a history of intracorneal tattooing several years previously were studied because of a significant change from their initial color. Each patient's file was reviewed with analysis of slit lamp photographs, OCT and specular microscopy., Results: All three patients experienced a significant color change in their tattoos between 5 and 6 years after surgery. The color had changed to golden-brown., Discussion: Retrospective analysis of the components of the tattoo ink found the presence of iron in the black pigment. We believe that pigments composed of iron oxide are transformed into golden-brown ferric iron oxide in the presence of oxygen in the aqueous environment. The presence of moderate corneal edema in these three cases of multioperated patients could explain, in these specific cases, the occurrence of oxidation typically not described., Conclusion: Corneal tattooing remains a simple and very interesting technique when partial or total absence of iris causes significant photophobia. However, the significant changes in color that we report more than 5 years later suggest omitting iron from the dyes used for the cornea and limiting its use in cases of limited endothelial prognosis. A long-term evaluation of corneal tattoos appears necessary., (Copyright © 2019. Published by Elsevier Masson SAS.)

Introduction: Corneal tattooing is a noninvasive technique which appears relatively well-tolerated in the medium term. We report the cases of 3 patients with a significant change in the color of their tattoos performed over 5 years previously., Patients and Methods: Three patients with a history of intracorneal tattooing several years previously were studied because of a significant change from their initial color. Each patient's file was reviewed with analysis of slit lamp photographs, OCT and specular microscopy., Results: All three patients experienced a significant color change in their tattoos between 5 and 6 years after surgery. The color had changed to golden-brown., Discussion: Retrospective analysis of the components of the tattoo ink found the presence of iron in the black pigment. We believe that pigments composed of iron oxide are transformed into golden-brown ferric iron oxide in the presence of oxygen in the aqueous environment. The presence of moderate corneal edema in these three cases of multioperated patients could explain, in these specific cases, the occurrence of oxidation typically not described., Conclusion: Corneal tattooing remains a simple and very interesting technique when partial or total absence of iris causes significant photophobia. However, the significant changes in color that we report more than 5 years later suggest removing iron from the dyes used for the cornea and limiting its use in cases of limited endothelial prognosis. A long-term evaluation of corneal tattoos appears necessary., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Purpose: To evaluate the safety and feasibility of intrastromal injection of human corneal stromal keratocytes (CSKs) and its therapeutic effect on a rodent early corneal opacity model., Methods: Twelve research-grade donor corneas were used in primary culture to generate quiescent CSKs and activated stromal fibroblasts (SFs). Single and repeated intrastromal injections of 2 to 4 × 104 cells to rat normal corneas (n = 52) or corneas with early opacities induced by irregular phototherapeutic keratectomy (n = 16) were performed, followed by weekly examination of corneal response under slit-lamp biomicroscopy and in vivo confocal microscopy with evaluation of haze level and stromal reflectivity, and corneal thickness using anterior segment optical coherence tomography (AS-OCT). Time-lapse tracing of Molday ION-labelled cells was conducted using Spectralis OCT and label intensity was measured. Corneas were collected at time intervals for marker expression by immunofluorescence, cell viability, and apoptosis assays., Results: Injected CSKs showed proper marker expression with negligible SF-related features and inflammation, hence maintaining corneal clarity and stability. The time-dependent loss of injected cells was recovered by repeated injection, achieving an extended expression of human proteoglycans inside rat stroma. In the early corneal opacity model, intrastromal CSK injection reduced stromal reflectivity and thickness, resulting in recovery of corneal clarity, whereas noninjected corneas were thicker and had haze progression., Conclusions: We demonstrated the safety, feasibility, and therapeutic efficacy of intrastromal CSK injection. The cultivated CSKs can be a reliable cell source for potential cell-based therapy for corneal opacities.

The clinical impact of microplasma jets on rabbit eyes infected by Candida albicans has been investigated. Arrays of such jets produce low-temperature plasma micro-columns suitable for ophthalmic therapeutics and fungal infections, in particular, and the technology is capable of being scaled to surface areas of at least 10 cm 2 . Keratitis was induced in the right central corneas of rabbits, whereas the left eyes served as a normal group. The rabbits were divided into the plasma non-treated group (control) and plasma treatment group. Histologic analyses of both groups showed marked reductions in the thickness, angiogenesis, and opacity of all rabbit corneas following plasma treatment. Indeed, for treatment times beyond 14 days, infected eyes exhibited no significant differences from the normal group. Healing of rabbit eyes infected by Candida albicans apparently proceeds by disrupting corneal epithelial proliferation, and by reducing fibrotic changes in the stroma. This study demonstrates that low-temperature plasma jets are remarkably effective in healing Candida albicans-infected corneas, thereby providing a promising medical treatment option for keratitis.

Purpose: We tested the potential of bone morphogenic protein 7 (BMP7) and hepatocyte growth factor (HGF) combination gene therapy to treat preformed corneal fibrosis using established rabbit in vivo and human in vitro models., Methods: Eighteen New Zealand White rabbits were used. Corneal fibrosis was produced by alkali injury. Twenty-four hours after scar formation, cornea received topically either balanced salt solution (BSS; n = 6), polyethylenimine-conjugated gold nanoparticle (PEI2-GNP)-naked plasmid (n = 6) or PEI2-GNP plasmids expressing BMP7 and HGF genes (n = 6). Donor human corneas were used to obtain primary human corneal fibroblasts and myofibroblasts for mechanistic studies. Gene therapy effects on corneal fibrosis and ocular safety were evaluated by slit-lamp microscope, stereo microscopes, quantitative real-time PCR, immunofluorescence, TUNEL, modified MacDonald-Shadduck scoring system, and Draize tests., Results: PEI2-GNP-mediated BMP7+HGF gene therapy significantly decreased corneal fibrosis in live rabbits in vivo (Fantes scale was 0.6 in BMP7+HGF-treated eyes compared to 3.3 in -therapy group; P < 0.001). Corneas that received BMP7+HGF demonstrated significantly reduced mRNA levels of profibrotic genes: α-SMA (3.2-fold; P < 0.01), fibronectin (2.3-fold, P < 0.01), collagen I (2.1-fold, P < 0.01), collagen III (1.6-fold, P < 0.01), and collagen IV (1.9-fold, P < 0.01) compared to the -therapy corneas. Furthermore, BMP7+HGF-treated corneas showed significantly fewer myofibroblasts compared to the -therapy controls (83%; P < 0.001). The PEI2-GNP introduced >104 gene copies per microgram DNA of BMP7 and HGF genes. The recombinant HGF rendered apoptosis in corneal myofibroblasts but not in fibroblasts. Localized topical BMP7+HGF therapy showed no ocular toxicity., Conclusions: Localized topical BMP7+HGF gene therapy treats corneal fibrosis and restores transparency in vivo mitigating excessive healing and rendering selective apoptosis in myofibroblasts.

Background: De Barsy syndrome is a rare, autosomal recessive syndrome characterized by cutis laxa, progeroid appearance, ophthalmic opacification, skeletal malformations, growth delays, and intellectual disability., Aims: The aim of this case series is to identify the anesthetic considerations in the clinical management of patients with de Barsy syndrome., Methods: A retrospective case review from 1968 to 2016 was performed at a single tertiary medical center to identify patients with de Barsy syndrome who underwent anesthesia for diagnostic and surgical procedures. We collected and analyzed the perioperative records and following data: age, sex, American Society of Anesthesiologists physical status, relevant comorbidities, surgical procedures, anesthesia management, and observed complications., Results: Three patients underwent 64 unique anesthetics for a diverse collection of diagnostic and surgical procedures. An array of anesthetics and techniques were successfully used. Observations of the perioperative period found 7 episodes of intraoperative hyperthermia (>38.3°), a single difficult airway requiring fiberoptic bronchoscopic-guided intubation, and repeatedly difficult intravenous access., Conclusion: This expanded case series suggests that providers caring for patients with de Barsy syndrome should be aware of potential challenges with airway management, vascular access, and temperature monitoring., (© 2017 John Wiley & Sons Ltd.)

Purpose: To report a case of wavelike interface opacities in a patient who underwent Descemet-stripping automated endothelial keratoplasty (DSAEK) and was managed conservatively over the course of 7 years., Methods: A 65-year-old woman underwent DSAEK for pseudophakic bullous keratopathy. Textural wavelike opacities were noted in the graft-host interface 6 days postoperatively without evidence of anterior segment inflammation. The patient's vision was also initially limited by the presence of cystoid macular edema (CME). Six months postoperatively, CME had resolved but the patient's vision failed to improve better than 20/80 because of the persistent dense interface opacities. The patient refused to undergo graft exchange despite a suboptimal visual result and she therefore was observed over time., Results: The interface opacities started to regress and her visual acuity improved to 20/30 by 9 months postoperatively. The opacities became gradually less prominent over the next few years, and at 7 years postoperatively, her best-corrected vision was 20/25., Conclusion: In this case, observation of this post-DSAEK complication rather than surgical intervention resulted in a favorable long-term visual outcome.

Objective: To describe clinical, in vivo confocal microscopic, histopathologic, and microbiologic features of canine and feline cases of infectious crystalline keratopathy (ICK)., Animals Studied: Six dogs and two cats with naturally acquired ICK., Procedures: Medical records of dogs and cats with a clinical diagnosis of ICK were reviewed. Signalment, medical history, clinical findings, and diagnostic evaluations were retrieved, including corneal cytology, histopathology, in vivo confocal microscopy, and microbiology results., Results: All animals presented with fine, needle-like, and branching white crystalline anterior stromal opacities emanating from corneal facets or corneal epithelial defects. Mild conjunctival hyperemia and anterior uveitis were frequently present. Concurrent ocular and systemic diseases were common, including keratoconjunctivitis sicca, corneal sequestrum, diabetes mellitus, hyperadrenocorticism, and malignant neoplasia. Bacteria, with minimal or absent leukocytes, were identified by cytology and histopathology. Histopathologically, the crystalline corneal opacities corresponded with dense accumulations of bacteria present in the interlamellar stromal spaces and forming cord-like projections within the stroma. In vivo confocal microscopy demonstrated deposits of reflective crystalline or amorphous structures within the stroma with a paucity of associated inflammatory changes. The most frequently cultured bacteria were alpha-hemolytic Streptococcus and Staphylococcus species. Resolution of clinical lesions was achieved in most cases with long-term medical or surgical therapy; however, the initiation of medical treatment was associated with an acute, dramatic onset of severe keratitis and anterior uveitis in some animals., Conclusions: Infectious crystalline keratopathy in dogs and cats shares many features with this condition in human patients. Prolonged medical therapy, or surgical intervention, is required for resolution., (© 2016 American College of Veterinary Ophthalmologists.)

Background Aims: Mesenchymal stromal cells (MSCs) offer tremendous potential for therapeutic applications for inflammatory diseases. However, tissue-derived MSCs, such as bone marrow-derived MSCs (BM-MSCs), have considerable donor variations and limited expandability. It was recently demonstrated that MSCs derived from induced pluripotent stem cells (iPSC-MSCs) have less pro-tumor potential and greater expandability of homogenous cell population. In this study, we investigated the anti-inflammatory effects and mechanism of iPSC-MSCs in a murine model of chemical and mechanical injury to the cornea and compared the effects with those of BM-MSCs., Methods: To create an injury, ethanol was applied to the corneal surface in mice, and the corneal epithelium was removed with a blade. Immediately after injury, mice received an intravenous injection of (i) iPSC-MSCs, (ii) BM-MSCs or (iii) vehicle. Clinical, histological and molecular assays were performed in the cornea to evaluate inflammation., Results: We found that corneal opacity was significantly reduced by iPSC-MSCs or BM-MSCs. Histological examination revealed that the swelling and inflammatory infiltration in the cornea were markedly decreased in mice treated with iPSC-MSCs or BM-MSCs. Corneal levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 were lower in iPSC-MSC- and BM-MSC-treated mice, compared with vehicle-treated controls. In contrast, iPSC-MSCs with a knockdown of the TNF-α stimulating gene (TSG)-6 did not suppress the levels of inflammatory cytokines and failed to reduce corneal opacity., Conclusions: Together these data demonstrate that iPSC-MSCs exert therapeutic effects in the cornea by reducing inflammation in part through the expression of TSG-6, and the effects are similar to those seen with BM-MSCs., (Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Salzmann's nodules comprise a heterogeneous group of greyish superficial corneal opacities. A substantial percentage is most likely caused by dystrophies. This could explain the recurrences after surgical removal. The Eye Center of the University Hospital Freiburg has been using mitomycin C intraoperatively during surgical removal of Salzmann's nodules since 2007 to prevent recurrences. We recently performed an uncontrolled prospective trial to evaluate this approach and also reviewed the literature. Worldwide, a total of 38 eyes have been treated with mitomycin C during surgery for Salzmann's nodules. No recurrences have been reported so far with follow-up exceeding at least 2 years in almost all eyes. No severe side effects have been observed to date. We therefore think that mitomycin C during surgery for Salzmann's nodules is advisable despite the lack of evidence from a randomized clinical trial. However, all patients must consent to the off label use of mitomycin C.

Peters anomaly is a form of anterior segment dysgenesis characterized by central ocular opacity and corneo-lenticular adhesions. Isolated and syndromic Peters anomaly can be observed and demonstrate significant genetic heterogeneity. We report the identification of overlapping 8q21.11 deletions in two patients with syndromic Peters anomaly via whole exome sequencing and chromosomal microarray analyses. Microdeletions of 8q21.11 were recently reported in 10 patients with highly variable phenotypes involving craniofacial features, ptosis, intellectual disability, abnormalities of the hands/feet and other defects; sclerocornea and/or microphthalmia were reported in three cases. The two additional cases presented in this report expand the phenotypic spectrum of 8q21.11 microdeletions to include Peters anomaly (seen in both patients) and persistent primary dentition (seen in one patient with a larger deletion). The two novel deletions include the ZFHX4 and PEX2 genes, which were also affected in all three previous cases involving ocular anomalies. Screening of the remaining alleles of ZFHX4 and PEX2 did not identify any additional likely pathogenic variants in either patient, suggesting a dominant mechanism (haploinsufficiency) for the identified deletion. This report provides further insight into the phenotypes associated with 8q21.11 deletions and, for the first time, reports Peters anomaly as an additional ocular feature; screening for copy number variations of the 8q21.11 region should be considered in patients with Peters anomaly and related syndromic features. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Importance: Corneal abrasion is the most common ocular complication associated with nonocular surgery, but toxic keratopathy is rare., Observation: Three patients developed severe toxic keratopathy after orofacial surgery on the left side with general anesthesia. All patients underwent surgery in the right lateral tilt position with ocular protection but reported irritation and redness in their right eyes after the operation. Alcohol-containing antiseptic solutions were used for presurgical preparation. Ophthalmic examination showed decreased visual acuity ranging from 20/100 to 20/400, corneal edema and opacity, anterior chamber reaction, or stromal neovascularization in the patients' right eyes. Confocal microscopy showed moderate to severe loss of corneal endothelial cells in all patients. Despite prompt treatment with topical corticosteroids, these 3 patients eventually required cataract surgery, endothelial keratoplasty, or penetrating keratoplasty, respectively. After the operation, the patients' visual acuity improved to 20/30 or 20/40. Data analysis was conducted from December 6, 2010, to June 15, 2015., Conclusions and Relevance: Alcohol-containing antiseptic solutions may cause severe toxic keratopathy; this possibility should be considered in orofacial surgery management. Using alcohol-free antiseptic solutions in the periocular region and taking measures to protect the dependent eye in the lateral tilt position may reduce the risk of severe corneal injury.

Purpose: To evaluate the visual outcomes, recurrence patterns, safety, and efficacy of excimer laser phototherapeutic keratectomy (PTK) in conjunction with mitomycin C (MMC) for corneal macular and granular diystrophies., Methods: The patients were divided into two groups. Group 1 included patients with macular corneal dystrophy (MCD) that caused superficial corneal plaque opacities, and Group 2 included patients with granular corneal dystrophy (GCD). Patients in both groups were pre-, peri-, and postoperatively evaluated. The groups were compared in terms of uncorrected visual acuity (VA), best spectacle-corrected VA, presence of mild or significant recurrence, and time of recurrence., Results: Eighteen eyes (nine with MCD and nine with GCD) of 18 patients (10 men and eight women) were included. PTK was performed for each eye that was included in this study. The mean ablation amount was 117.8 ± 24.4 µm and 83.5 ± 45.7 µm in MCD and GCD, respectively, (p=0.18). The postoperative improvement of the mean VA was similar between the two groups before recurrences (p>0.43) and after recurrences (p>0.71). There were no statistically significant differences in the recurrence rate and the recurrence-free period for any recurrence type., Conclusion: PTK was an effective, safe, and minimally invasive procedure for patients with MCD and GCD. PTK in conjunction with MMC was similarly effective for both groups in terms of recurrence and visual outcomes.

The aim of this study was to examine whether mesenchymal stem cells (MSCs) and/or corneal limbal epithelial stem cells (LSCs) influence restoration of an antioxidant protective mechanism in the corneal epithelium and renewal of corneal optical properties changed after alkali burns. The injured rabbit corneas (with 0.25 N NaOH) were untreated or treated with nanofiber scaffolds free of stem cells, with nanofiber scaffolds seeded with bone marrow MSCs (BM-MSCs), with adipose tissue MSCs (Ad-MSCs), or with LSCs. On day 15 following the injury, after BM-MSCs or LSCs nanofiber treatment (less after Ad-MSCs treatment) the expression of antioxidant enzymes was restored in the regenerated corneal epithelium and the expressions of matrix metalloproteinase 9 (MMP9), inducible nitric oxide synthase (iNOS), α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), and vascular endothelial factor (VEGF) were low. The central corneal thickness (taken as an index of corneal hydration) increased after the injury and returned to levels before the injury. In injured untreated corneas the epithelium was absent and numerous cells revealed the expressions of iNOS, MMP9, α-SMA, TGF-β1, and VEGF. In conclusion, stem cell treatment accelerated regeneration of the corneal epithelium, restored the antioxidant protective mechanism, and renewed corneal optical properties.

As our understanding of phenotype has improved with improving anterior segment imaging, it has become increasingly clear that the early genotype-phenotype correlations were largely misled by inaccurate phenotyping. Using a novel classification, congenital or neonatal corneal opacification can be considered to be primary or secondary. Secondary corneal disease may be developmental or acquired. Genetic analysis using this phenotypic classification becomes easier to navigate. Primary corneal disease includes endothelial dystrophies, corneal dermoids, cornea plana, and CYP1B1 cytopathy. Genotyping for all these conditions is reasonably advanced. Secondary developmental corneal disease includes entities that are the least well understood genotypically. These are kerato-irido-lenticular dysgenesis (also known as Peters anomaly, types 1 and 2). The genotyping literature of these conditions is littered with confusion. Iridocorneal adhesions (Peters anomaly 1) are often avascular, whereas keratolenticular adhesions (Peters anomaly 2) are usually vascularized. Children with a known molecular diagnosis can have iridocorneal adhesion in one eye and keratolenticular adhesion in the other eye. This further supports the notion that Peters anomaly 1 or 2 is a sign and not a diagnosis. Further types of kerato-irido-lenticular dysgenesis are those in which the lens fails to form or forms and then degenerates. Genotyping in these cases has been somewhat more fruitful but, as always, not comprehensive. If the lens fails to form or forms partially, the gene involved is FOXE3, which is a lens gene. Not surprisingly, if the lens forms partially or fails to form, this has an effect on the vitreous and the drainage angle. These cases are often associated with severe glaucoma. Other secondary developmental corneal diseases may include Axenfeld-Rieger syndrome, Aniridia, and primary congenital glaucoma, all of which have specific genotypic characterization. Other secondary causes are acquired and include infection, trauma, and metabolic disorders.

Purpose: To evaluate the efficacy of mesenchymal stem cells (MSCs) to ameliorate the consequences of corneal alkali injuries., Methods: Corneal alkali injuries were created in 30 rabbit eyes. The MSC group (n = 15) were treated with intrastromal and subconjunctival injections of phosphate-buffered saline (PBS) containing 2 × 10(6) MSCs and topical application. The control group (n = 15) was treated with PBS by the same applications forms. Drops of standard treatment (ascorbate 10 %, citrate 10 %, tobramycin, dexamethasone, Cyclogyl) were instilled for 2 weeks. Rabbits underwent slit-lamp examination, fluorescein staining, photography, and were evaluated for corneal neovascularization, opacification, and epithelial defects. Tear secretion and IOP were also evaluated. Furthermore, the concentration of Serumglutamic-pyruvic transaminase (SGPT) and vascular endothelial factor (VEGF) were measured. Immunohistochemistry was also performed for a-SMA and Ki-67., Results: Eyes treated with MSCs showed better recovery. The mean neovascularized area was significantly smaller in the MSC group (p < 0.05). A significant difference in the degree of corneal opacification and re-epithelialization was also observed, as well as the IOP at 21 and 28 posttraumatic days (p < 0.05). Histology showed that MSCs resulted in almost normal architecture of eye tissues. After the MSCs infusion, SGPT and VEGF levels in cornea were significantly reduced. Immunohistochemistry demonstrated a reduction of a-SMA in the MSC group with higher mitotic-regenerative activity with the presence of Ki67., Conclusions: Our study represents a first step in understanding the possibilities of the MSC approach to treatment of alkali injuries of the cornea and shows that such an approach improves clinical outcomes and leads to better prognosis.

Background: Trachomatous trichiasis (TT) needs to be managed to reduce the risk of vision loss. The long-term impact of epilation (a common traditional practice of repeated plucking of lashes touching the eye) in preventing visual impairment and corneal opacity from TT is unknown. We conducted a randomized controlled trial of epilation versus surgery for the management of minor TT (fewer than six lashes touching the eye) in Ethiopia. Here we report the four-year outcome and the effect on vision and corneal opacity., Methodology/ Principal Findings: 1300 individuals with minor TT were recruited and randomly assigned to quality trichiasis surgery or repeated epilation using high quality epilation forceps by a trained person with good near vision. Participants were examined six-monthly for two-years, and then at four-years after randomisation. At two-years all epilation arm participants were offered free surgery. At four-years 1151 (88.5%) were re-examined: 572 (88%) and 579 (89%) from epilation and surgery arms, respectively. At that time, 21.1% of the surgery arm participants had recurrent TT; 189/572 (33%) of the epilation arm had received surgery, while 383 (67%) declined surgery and had continued epilating ("epilation-only"). Among the epilation-only group, 207 (54.1%) fully controlled their TT, 166 (43.3%) had minor TT and 10 (2.6%) had major TT (&gt;5 lashes). There were no differences between participants in the epilation-only, epilation-to-surgery and surgery arm participants in changes in visual acuity and corneal opacity between baseline and four-years., Conclusions/ Significance: Most minor TT participants randomised to the epilation arm continued epilating and controlled their TT. Change in vision and corneal opacity was comparable between surgery and epilation-only participants. This suggests that good quality epilation with regular follow-up is a reasonable second-line alternative to surgery for minor TT for individuals who either decline surgery or do not have immediate access to surgical treatment.

Purpose: To evaluate the efficacy and safety of transepithelial collagen cross-linking by iontophoretic delivery of riboflavin in treatment of progressive keratoconus., Methods: Eleven patients (15 eyes) with progressive keratoconus were enrolled. After 0.1% riboflavin-distilled water solution was deliveried via transepithelial iontophpresis for 5 min with 1 mA current, and ultraviolet radiation (370 nm, 3 mW/cm2) was performed at a 1.5 cm distance for 30 min. The follow up were 6 months in all eyes. The uncorrected visual acuity, corrected visual acuity, endothelial cell counting, corneal thickness, intraocular pressure, corneal curvature, corneal topography, OCT and corneal opacity before and 6-month after surgery were analyzed., Results: At 6 month postoperatively, mean uncorrected visual acuity and corrected visual acuity changed from 0.36 to 0.30 and from 0.42 to 0.57 without statistical significance. The mean value of each index of corneal curvature declined without statistical significance.Kmax value dereased from 60.91 to 59.91, and the astigmatism declined from 3.86 to 3.19. Central corneal thickness decreased from 460.93 μm to 455.40 μm, and thinnest corneal thickness declined from 450.87 μm to 440.60 μm with no statistical significance. Intraocular pressure was significantly elevated from 10.85 mmHg to 12.62 mmHg. Endothelial cell count did not change significantly. No corneal haze occurred. Mean depth of corneal demarcation line was 288.46 μm at 1 month postoperatively., Conclusion: Transepithelial corneal collagen cross-linking by iontophoresis is effective and safe in the treatment of progressive keratoconus, and yields stable clinical outcomes during 6-month follow up. However, long-term follow up is urgently required.

Purpose: Wound induced corneal fibrosis can lead to permanent visual impairment. Keratocyte activation and differentiation play a key role in fibrosis, and vimentin, a major structural type III intermediate filament, is a required component of this process. The purpose of our study was to develop a nonviral therapeutic strategy for treating corneal fibrosis in which we targeted the knockdown of vimentin., Methods: To determine the duration of plasmid expression in corneal keratocytes, we injected a naked plasmid expressing green fluorescent protein (GFP; pCMV-GFP) into an unwounded mouse corneal stroma. We then injected pCMV-GFP or plasmids expressing small hairpin RNA in the corneal wound injury model (full-thickness corneal incision) to evaluate opacification., Results: GFP expression peaked between days 1 and 3 and had prominent expression for 15 days. In the corneal wound injury model, we found that the GFP-positive cells demonstrated extensive dendritic-like processes that extended to adjacent cells, whereas the vimentin knockdown model showed significantly reduced corneal opacity., Conclusions: These findings suggest that a nonviral gene therapeutic approach has potential for treating corneal fibrosis and ultimately reducing scarring., (Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.)

Corneal transparency is maintained, in part, by specialized fibroblasts called keratocytes, which reside in the fibrous lamellae of the stroma. Corneal clouding, a condition that impairs visual acuity, is associated with numerous diseases, including mucopolysaccharidosis (MPS) type VII. MPS VII is due to deficiency in β-glucuronidase (β-glu) enzymatic activity, which leads to accumulation of glycosaminoglycans (GAGs), and secondary accumulation of gangliosides. Here, we tested the efficacy of canine adenovirus type 2 (CAV-2) vectors to transduce keratocyte in vivo in mice and nonhuman primates, and ex vivo in dog and human corneal explants. Following efficacy studies, we asked if we could treat corneal clouding by the injection a helper-dependent (HD) CAV-2 vector (HD-RIGIE) harboring the human cDNA coding for β-glu (GUSB) in the canine MPS VII cornea. β-Glu activity, GAG content, and lysosome morphology and physiopathology were analyzed. We found that HD-RIGIE injections efficiently transduced coxsackievirus adenovirus receptor-expressing keratocytes in the four species and, compared to mock-injected controls, improved the pathology in the canine MPS VII cornea. The key criterion to corrective therapy was the steady controlled release of β-glu and its diffusion throughout the collagen-dense stroma. These data support the continued evaluation of HD CAV-2 vectors to treat diseases affecting corneal keratocytes., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Introduction: Available data on traumatic cataract in Asian children is primarily confined to South Asian countries. We aimed to describe the demographics, nature of injury and visual outcomes of Malaysian children with traumatic cataract from a suburban area, and discuss the literature on Asian children with this condition., Methods: We conducted a retrospective study of 29 children below 17 years of age who were diagnosed with traumatic paediatric cataract and who attended Hospital Universiti Sains Malaysia, Kelantan, Malaysia, between January 2000 and December 2010. Follow-up periods ranged from 12 to 120 months. Demographic data, clinical features, mechanism and extent of injury, and final visual outcome were recorded., Results: The study population was predominantly male. The right eye was injured in 62.07% of patients. A majority of patients had penetrating injuries, with the most common cause being injury by an organic foreign body (24.14%). Presenting visual acuity worse than 6/60 was observed in 68.97% of patients. Only 34.48% of patients had a final corrected visual acuity of 6/12 and better. 55.18% of patients were operated on within less than one month of their injuries. A majority of children sustained concurrent injuries to the anterior segment structures. Corneal opacity and amblyopia were the most common causes of poor final visual acuity., Conclusion: Health education and awareness are essential tools that can prevent avoidable blindness due to traumatic cataract in the paediatric population. The importance of rehabilitation programmes for these patients should be emphasised.

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., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Purpose: To report corneal abnormalities and confocal microscopy findings in a patient with a variant of Gaucher disease (GD)., Methods: Case report with slit-lamp photography, confocal microscopy, and molecular analysis of the glucocerebrosidase gene., Results: Ophthalmic evaluation in a 57-year-old white patient demonstrated corneal opacities scattered throughout the cornea. Confocal microscopy revealed a completely distorted stromal architecture. The anterior part showed keratocytes with an abnormal morphology intermingled with minute white dots. In the posterior part, normal keratocytes were virtually absent and replaced by hyperreflective rod-like structures. Analysis of the glucocerebrosidase gene disclosed a heterozygous F216Y/L444P mutation. The patient's old records revealed that these corneal abnormalities were already present at the age of 16 years, almost 15 years before the diagnosis of GD was made. His 2 siblings known with the same disorder and mutations also showed abnormal visual acuity and increased central corneal thickness. The confocal microscopy demonstrated some subclinical abnormalities, but otherwise normal corneas., Conclusions: Our patient had an unusual mutation responsible for his GD. Although corneal opacities are virtually unknown in GD, except in the D409H homozygous cardiovascular subtype, this patient had marked corneal stromal abnormalities.

Purpose: To describe 3 cases with deep corneal stromal opacity that occurred several months after corneal cross-linking., Methods: A 36-year-old man, a 19-year-old man, and a 14-year-old girl underwent corneal cross-linking for their progressive keratoconus. Corneal cross-linking was performed according to the Dresden protocol. The corneal epithelium was ablated using an excimer laser in 2 cases and manually in 1 case. After 30 minutes of riboflavin presoaking, hypotonic riboflavin solution was applied until the corneal stroma swelled, after which the eyes were exposed to ultraviolet irradiation. Slit-lamp microscopy findings, uncorrected visual acuity, best-corrected visual acuity, manifest refraction, intraocular pressure, and corneal endothelial cell counts were evaluated, and corneal topography with Scheimpflug imaging was performed., Results: In all cases, the epithelium healed without delay. All eyes showed mild stromal infiltration a few days after the procedure; however, the inflammation was resolved within 1 week. The corneal stroma revealed no opacity up to 1 month after the procedure. A deep stromal opacity that extended to the inferior paracentral area developed after a few months and remained for 6 months to 1 year. Because the opacity was not on the visual axis, the visual acuity was not involved., Conclusions: Deep stromal opacity developed several months after uneventful corneal cross-linking. Postoperative inflammation may play a crucial role in its pathogenesis.

Many systemic lysosomal storage disorders show basic corneal opacities already in childhood. The lysosome is a cell organelle, produced by Golgi's apparatus, that is surrounded by a membrane and contains hydrolytic enzymes that break down food molecules, especially proteins and other complex molecules. The ophthalmologist's precise diagnosis of corneal clouding at the slit-lamp may reveal the correct interpretation of the specific lysosomal storage disorder. It is very important to diagnose such diseases as soon as possible because today the development of systemic enzymatic therapies has broadened the therapeutic armamentarium for the current standard of care. The following corneal landmarks of systemic storage diseases and of the modern systemic therapy are presented: cornea verticillata in Fabry's disease, periodic infusion of alpha-galactosidase a; Kayser-Fleischer's ring in Wilson's disease, zinc, trienetin, low copper diet; multiple, punctiform crystals in cystinosis, cysteamine, Raptor RP 103(DR cysteamine) that reduces the cytotoxity in form of continous dissolving of cystine from lysosome, renal transplantation, haematopoietic stem cell transplantation; peripheral ring, but not true lipid arc, and moderate stromal haze in LCAT-deficiency, injection of recombinant enzyme or of encapsulated LCAT-secreting cells; diffuse stromal haze in mucopolysaccharidoses (MPS). Enzyme replacement therapy is currently indicated for MPS I, MPS II, and MPS VI, haematopoietic stem cell transplantation; painful, bilateral pseudo-dendritic opacities in tyrosinemia type II (eponym: Richner-Hanhart syndrome), low phenylalanine and tyrosine diet result in complete disappearance of corneal alterations with a consecutive painfree period. Strict diet during the whole life is necessary to prevent corneal recurrences and the occurrence of palmo-plantar keratoses. Such therapies can enable the patient to lead an otherwise normal life for decades., (Georg Thieme Verlag KG Stuttgart · New York.)

Unlabelled: An 86-year-old patient developed a significant intraocular inflammatory reaction after having phacoemulsification. Topical therapy did not eliminate the inflammation, and tissue plasminogen activator (tPA) was injected into the anterior chamber. A white corneal plaque appeared in the previously clear cornea within days of the injection. The lesion was diagnosed as calcific band keratopathy and successfully treated with ethylenediaminetetraacetic acid chelation. Electron microscopy and elemental analysis of a corneal scraping from the lesion established its composition to be mainly calcium and phosphate, validating the diagnosis. This is the seventh reported case of rapid formation of calcific band keratopathy after tPA injection. The pathogenesis of this rare complication involves multiple factors, including alkalinization of the intraocular pH, increased phosphate concentration, and endothelial dysfunction., Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned., (Copyright © 2013 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

According to the World Health Organization, 5.1% of blindnesses or visual impairments are related to corneal opacification. Cornea is a transparent tissue placed in front of the color of the eye. Its transparency is mandatory for vision. The ocular surface is a functional unit including the cornea and all the elements involved in maintaining its transparency i.e., the eyelids, the conjunctiva, the lymphoid tissue of the conjunctiva, the limbus, the lacrymal glands and the tear film. The destruction of the ocular surface is a disease caused by : traumatisms, infections, chronic inflammations, cancers, toxics, unknown causes or congenital abnormalities. The treatment of the ocular surface destruction requires a global strategy including all the elements that are involved in its physiology. The microenvironnement of the ocular surface must first be restored, i.e., the lids, the conjunctiva, the limbus and the structures that secrete the different layers of the tear film. In a second step, the transparency of the cornea can be reconstructed. A corneal graft performed in a healthy ocular surface microenvironnement will have a better survival rate. To achieve these goals, a thorough understanding of the renewal of the epitheliums and the role of the epithelial stem cells are mandatory., (© Société de Biologie, 2013.)

Purpose: To describe a cause and management of interface haze after Descemet stripping endothelial keratoplasty (DSEK)., Methods: Five patients underwent uncomplicated combined DSEK/phacoemulsification with intraocular lens implantation at a tertiary referral center over a span of 3 months. In each case, the recipient Descemet membrane was stripped with the anterior chamber filled with a cohesive viscoelastic. Patients subsequently developed visually significant haze in the graft-host interface that had a fine reticular pattern. Examination also revealed a small separation between the donor and recipient cornea in 3 cases. In all cases, there was no communication between the area of detachment and the anterior chamber, and the overlying recipient cornea was clear. Clinical and imaging findings of the interface haze suggested that it was the result of retained viscoelastic in the interface. Patients were either observed or underwent surgery to irrigate the viscoelastic from the interface., Results: Of the 5 patients, 3 were simply observed with eventual clearing of the haze and attainment of best-corrected visual acuity of 20/40 or better. Two patients with more extensive interface haze and visible space on slit examination between the donor and recipient cornea underwent irrigation and aspiration of the graft-host interface, with quick resolution of the haze. All grafts remained clear at the last follow-up., Conclusions: Retained viscoelastic at the graft-host interface during DSEK can cause a reticular interface haze that can compromise visual clarity. The haze can be eliminated by irrigating and aspirating the graft-host interface with improvement in vision. Careful irrigation and aspiration of viscoelastic from the posterior corneal surface of the recipient at the time of endothelial keratoplasty can prevent this form of interface haze.

Purpose: Rapid assessment of cicatricial trachoma in adult females aged over 15 years in a previously hyperendemic rural area in Haryana, North India., Methods: Ten disadvantaged villages each with a population of 3000-5000 were chosen by cluster random sampling. One thousand females, 500 between 15-30 years and the rest over 30 years in the underdeveloped parts of the villages, identified by observation and consultation, were examined for signs of trachomatous scarring (TS), trachomatous trichiasis (TT) and trachomatous corneal opacity (TCO). Examinations of both eyes were performed with the aid of a binocular loupe (2.5x magnification) for signs of trachoma, its complications and other ocular morbidities., Results: Bilateral examination was carried out in all participants. About two-thirds (n = 650; 65%) of subjects did not have any signs of trachoma. The percentages of trachoma stages TS, TT and TCO were found to be 26.4%, 5.4% and 3.2% respectively. Trichiasis was observed in 54 subjects, all in the age group >30 years, and highest in the age group 66-75 years (22.8%). Females in the age group >30 years had significantly higher cicatricial trachoma compared to females <30 years (p < 0.001). Overall 59.3% of affected females had not received any treatment. Epilation and entropion surgery had been performed in 30.3% and 10.4% of affected females, respectively., Conclusion: The results of our rapid assessment suggest that the presence of cicatricial trachoma remains an important health issue in females over 15 years of age.

Background/aims: To assess corneal refraction and axial length in children with mucopolysaccharidosis I-Hurler (MPS I-H), treated early with stem cell transplantation (SCT), in order to establish possible causes of hyperopia., Methods: Clinical ophthalmological follow-up included keratometry and measurements of axial length., Results: Five patients, with SCT performed before 23 months of age, were examined. Median age was 8.2 years (range 5.2-10.5). Best-corrected decimal visual acuity was ≥ 0.5 (≥ 20/40 Snellen fraction) in seven of 10 eyes. High hyperopia, ranging from +4.0 to +9.0 spherical equivalents, was noted in all 10 eyes. Mild to moderate corneal opacities occurred in all 10 eyes. Optic disc areas, borders and cuppings were normal in all 10 eyes. No patient had glaucoma. Keratometry could be performed in five patients and demonstrated low values in the group ranging from 38.24 to 41.56 Diopters (D) right eye to 38.24-41.94 D left eye, which was significantly lower than the age matching reference material (p < 0.05). Axial lengths, available in five patients, ranged between 20.68 to 21.57 mm right eye and 20.52 to 21.38 mm left eye, which also was lower than the age matching reference material (p < 0.05)., Conclusion: Reduced axial length together with reduced corneal refraction is suggested to be causative to the hyperopia in patients with MPS I Hurler. Detection of refractive errors and prescription of eye glasses are important to avoid amblyopia., (© 2010 The Authors. Journal compilation © 2010 Acta Ophthalmol.)

Previous reports demonstrated that the deleterious effects of chemical injury to the cornea were ameliorated by local or systemic administration of adult stem/progenitor cells from bone marrow referred to as mesenchymal stem or stromal cells (MSCs). However, the mechanisms for the beneficial effects of MSCs on the injured cornea were not clarified. Herein, we demonstrated that human MSCs (hMSCs) were effective in reducing corneal opacity and inflammation without engraftment after either intraperitoneal (i.p.) or intravenous (i.v.) administration following chemical injury to the rat cornea. A quantitative assay for human mRNA for glyceraldehyde 3-phosphate dehydrogenase (GAPDH) demonstrated that less than 10 hMSCs were present in the corneas of rats 1-day and 3 days after i.v. or i.p. administration of 1 × 10(7) hMSCs. In vitro experiments using a transwell coculture system demonstrated that chemical injury to corneal epithelial cells activated hMSCs to secrete the multipotent anti-inflammatory protein TNF-α stimulated gene/protein 6 (TSG-6). In vivo, the effects of i.v. injection of hMSCs were largely abrogated by knockdown of TSG-6. Also, the effects of hMSCs were essentially duplicated by either i.v. or topical administration of TSG-6. Therefore, the results demonstrated that systemically administered hMSCs reduce inflammatory damage to the cornea without engraftment and primarily by secretion of the anti-inflammatory protein TSG-6 in response to injury signals from the cornea., (Copyright © 2011 AlphaMed Press.)

Unlabelled: We report a case of bilateral corneal opacities in a laser in situ keratomileusis (LASIK) patient who subsequently had carbon dioxide (CO(2)) laser skin resurfacing. The presumed etiology of the visually significant corneal opacities was late-onset diffuse lamellar keratitis (DLK), secondary to traumatic corneal abrasions from the use of metal eye shields. The DLK went untreated for 1 month, resulting in permanent interface scarring and a corrected distance visual acuity of 20/30 in the patient's right eye and 20/20 in the left eye. We think patients who have had LASIK and are planning to have CO(2) laser skin resurfacing or any procedure that uses protective metal eye shields should be counseled about the risk for late-onset DLK as a potential complication. This warning is particularly germane now as an increasing number of patients who have had LASIK are entering the decades of life when cosmetic surgery is most likely to be sought., Financial Disclosure: Neither author has a financial or proprietary interest in any material or method mentioned., (Copyright © 2011 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess the visual outcome of using fibrin adhesive in automated lamellar therapeutic keratoplasty with a microkeratome in the treatment of anterior corneal opacities., Methods: In this prospective noncomparative clinical trial, surgery was done on 10 eyes belonging to 9 patients with anterior stromal opacity (macular dystrophy, spheroidal degeneration, scarring because of advanced recurrent pterygium, refractive surgery, or trauma). Depending on the depth of the opacity, a 130- or 250-μm flap was removed from the recipient cornea using a microkeratome. Then, a thin layer of fibrin adhesive was spread over the bed, and a lenticule with the same thickness, created from the donor cornea, was positioned in place. After allowing the glue to set for about 5 minutes, a bandage contact lens was placed over the cornea, which was removed 7-10 days postoperatively., Results: All corneas healed properly, and none required suturing or reoperation. During the follow-up period, no inflammation or rejection was observed. The donor cornea and the donor-recipient interface remained clear in all cases. The mean of best contact lens-corrected visual acuity improved from 1.14 ± 0.53 to 0.51 ± 0.23 in the logarithm of the minimum angle of resolution scale., Conclusions: The fibrin glue can provide safe and effective attachment needed in automated lamellar therapeutic keratectomy and obviates the need for suturing. However, it requires improvement for easier and safer use in ophthalmology.

Ocular pathology is common in patients with mucopolysaccharidosis (MPS), a hereditary lysosomal storage disorder, where the eye as well as other tissues accumulate excessive amounts of glycosaminoglycans. Despite genetic and phenotypic heterogeneity within and between different types of MPS, the disease symptoms and clinical signs often manifest during the first 6 months of life with increasing head size, recurrent infections, umbilical hernia, growth retardation and skeletal problems. Typical ocular features include corneal clouding, ocular hypertension/glaucoma, retinal degeneration and optic nerve atrophy. Visual deterioration and sensitivity to light may substantially reduce the quality of life in MPS patients, particularly when left untreated. As an early intervention, haematopoietic stem cell transplantation and/or enzyme replacement therapy are likely to improve patients' symptoms and survival, as well as visual outcome. Thus, it is of utmost importance to ensure proper detection and accurate diagnosis of MPS at an early age. It is of fundamental value to increase awareness and knowledge among ophthalmologists of the ocular problems affecting MPS patients and to highlight potential diagnostic pitfalls and difficulties in patient care. This review provides insight into the prevalence and severity of ocular features in patients with MPS and gives guidance for early diagnosis and follow-up of MPS patients. MPS poses therapeutic challenges in ocular management, which places ophthalmologists next to paediatricians at the forefront of interventions to prevent long-term sequelae of this rare but serious disease.

Once a corneal scar develops, surgical management remains the only option for visual rehabilitation. Corneal transplantation is the definitive treatment for a corneal scar. In addition to the challenges posed by graft rejections and other postoperative complications, the lack of high-quality donor corneas can limit the benefits possible with keratoplasty. The purpose of our study was to evaluate a new therapeutic strategy for treating corneal scarring by targeting collagen deposition. We overexpressed a fibril collagenase (matrix metalloproteinase 14 (MMP14)) to prevent collagen deposition in the scar tissue. We demonstrated that a single and simple direct injection of recombinant adeno-associated virus-based vector expressing murine MMP14 can modulate gene expression of murine stromal keratocytes. This tool opens new possibilities with regard to treatment. In a mouse model of corneal full-thickness incision, we observed that MMP14 overexpression reduced corneal opacity and expression of the major genes involved in corneal scarring, especially type III collagen and α-smooth muscle actin. These results represent proof of concept that gene transfer of MMP14 can reduce scar formation, which could have therapeutic applications after corneal trauma.