A novel method of evaluating the non-invasive tear film break-up time and progression of corneal opacification in dogs using imaging video.

This study aimed to determine the correlation of the parameters that indicate the status of the ocular surface with the prognosis of corneal opacification. Fifty dogs (96 eyes) were examined using a grid-line illuminator (non-invasive tear film break-up time (NIBUT)). Thirty dogs (54 eyes) were included in the final analysis based on the criteria. The NIBUT and tear film break-up time (TFBUT) results of the eyes included in the study were divided into three groups: Group 1 (< 5 s), Group 2 (5 to <10 s), and Group 3 (≥ 10 s). The Schirmer's tear Test 1 (STT-1) results of the included patients were also divided into three groups: Group 1 (< 5 mm/min), Group 2 (5 to <10 mm/min), and Group 3 (≥ 10 mm/min). The corneal opacity grades are divided into four scores, ranging from 0 to 3. The corneal opacity grade score (COS) of 0 indicates a completely clear cornea or only a trace of opacity. COS of 1, 2, 3 indicate the presence of a prominent corneal opacity that does not interfere with the visualization of the fine iris details, the opacity obscures the visibility of the iris and lens details and severe obstruction of the intraocular structure visibility, respectively. The mean difference in COS during the follow-ups for each group of NIBUT were 0.61 ± 0.92 (n = 28), 0.10 ± 0.32 (n = 10), 0.19 ± 0.40 (n = 16). The NIBUT groups were significantly correlated with COS (p-value = 0.073) at a 10% level of significance. Post-hoc test at a 10% level of significance revealed significant correlations between Groups 1 and 2 (p-value = 0.041) and between Groups 1 and 3 (p-value 0.104). Although the TFBUT and STT-1 groups did not show any significant correlation with COS. Eyes with NIBUT of <5 s were found to have a significantly higher chance of increased COS compared with eyes with NIBUT of >5 s in the grid-line illumination plate NIBUT test. Among NIBUT, STT-1, and TFBUT, NIBUT was the only test that showed significant associations with the changes in COS.

Peripheral hypertrophic subepithelial corneal opacification - Role of tear secretion, medication and systemic diseases.

BACKGROUND: Peripheral hypertrophic subepithelial corneal opacification (PHSCO) is a corneal disease that may severely affect vision. The major goal of this study was to test the hypothesis that tear secretion, medication and systemic diseases are associated with PHSCO. METHODS: This is a retrospective, case-control study conducted at the Department of Ophthalmology, University Medical Center of the Johannes Gutenberg University Mainz. We analysed medical records of patients diagnosed with PHSCO. Sex, age, Schirmer's test II, general medication and medical history were assessed and compared to an age- and sex-matched control group from the Gutenberg Health Study (GHS). RESULTS: One hundred ninety-five eyes of 112 patients with PHSCO were included. Eighty-eight patients were female with a mean age of 55.3 ± 14.7 years (23-89 years) and 24 patients were male with a mean age of 59.3 ± 12.6 years (38-84 years). In 83 patients (74.1%) both eyes were involved. The Schirmer's test II was significantly reduced in patients with PHSCO compared to the GHS control group (p < 0.001). Patients with PHSCO were more frequently administered artificial tears and steroid eye drops (p < 0.001) and were more hyperopic than healthy controls (p = 0.01). Systemic diseases or medication did not differ markedly between PHSCO and healthy controls. CONCLUSION: Reduced tear secretion and more frequent use of artificial tears in patients with PHSCO suggest a link between PHSCO and dry eye disease. The results of the study do not support our hypothesis that PHSCO is associated with systemic diseases. Interestingly, patients with PHSCO were less frequently on ß-blockers than control subjects.

Biomarkers of Glycosaminoglycans (GAG) accumulation in patients with mucopolysaccharidosis type VI-LeukoGAG, Corneal Opacification (COM) and Carotid Intima Media Thickening (CIMT).

Mucopolysaccharidosis type VI (MPS VI) is an autosomal recessive lysosomal storage disorder characterized by deficient activity of arylsulfatase B enzyme (ASB) resulting in cellular accumulation of dermatan sulfate (DS) and chondroitin sulfate (CS) that leads to cell injury. Urinary glycosaminoglycans (GAG) are often used as a biomarker in MPS diseases for diagnosis and to monitor treatment efficacy. This study evaluated leukocyte GAGs (leukoGAG) and skin GAGs as alternate biomarkers representing intracellular GAG changes in patients with MPS VI and treated with enzyme replacement therapy (ERT). In addition, we evaluated corneal opacification measurements (COM) and carotid intima media thickness (CIMT) as indicators of GAG accumulation and tissue injury. The study was performed in a serial two-step design in a single center. A quantitative method to measure leukoGAG levels in leukocytes was developed in Study 1 to compare the GAG levels between MPS VI patients and a control group and to assess correlations between leukoGAG and urineGAG. Study 2 validated the leukoGAG measurement, assessed the effect of ERT infusion on leukoGAG and ASB activity in leukocytes, identified correlations between leukoGAG and other biomarkers, and assessed differences in GAG accumulation between MPS VI patients and control subjects. In Study 1, leukoCS and leukoDS levels were significantly higher in the MPS VI group than the control group (leukoCS: 37.9 ± 10.2 and 2.9 ± 1.5 µg/µg protein, respectively, p = 0.005; leukoDS: 0.26 ± 0.2 and 0.0 ± 0.0 µg/µg protein, respectively, p = 0.028) with positive correlations between leukoCS and urine CS and leukoDS and urineDS. In Study 2, leukoCS (32.0 ± 11.8 vs 6.9 ± 3.1 µg/mg protein, p = 0.005) and leukoDS (0.4 ± 0.1 and 0.2 ± 0.1 µg/mg protein, p = 0.020) were significantly higher compared with control subjects. Thus, these results highlight the potential of leukoGAG as a new biomarker representing intracellular GAG accumulation in MPS VI patients and may be valuable for patient management.

A Novel 13q12 Microdeletion Associated with Familial Syndromic Corneal Opacification.

Progressive corneal opacification can result from multiple etiologies, including corneal dystrophies or systemic and genetic diseases. We describe a novel syndrome featuring progressive epithelial and anterior stromal opacification in a brother and sister and their mildly affected father, with all three family members having sensorineural hearing loss and two also with tracheomalacia/laryngomalacia. All carried a 1.2 Mb deletion at chromosome 13q12.11, with no other noteworthy co-segregating variants identified on clinical exome or chromosomal microarray. RNAseq analysis from an affected corneal epithelial sample from the proband's brother revealed downregulation of XPO4, IFT88, ZDHHC20, LATS2, SAP18, and EEF1AKMT1 within the microdeletion interval, with no notable effect on the expression of nearby genes. Pathway analysis showed upregulation of collagen metabolism and extracellular matrix (ECM) formation/maintenance, with no significantly down-regulated pathways. Analysis of overlapping deletions/variants demonstrated that deleterious variants in XPO4 were found in patients with laryngomalacia and sensorineural hearing loss, with the latter phenotype also being a feature of variants in the partially overlapping DFNB1 locus, yet none of these had reported corneal phenotypes. Together, these data define a novel microdeletion-associated syndromic progressive corneal opacification and suggest that a combination of genes within the microdeletion may contribute to ECM dysregulation leading to pathogenesis.

A Review of Monkeypox Ocular Manifestations and Complications: Insights for the 2022 Outbreak.

Monkeypox (MPVX) infection has been associated with multiorgan presentations. Thus, monkeypox infection's early and late complications are of particular concern, prompting health systems to decipher threatening sequels and their possible countermeasures. The current article will review the clinical signs and symptoms of the present and former outbreaks, differential diagnoses, workup and treatment of the ocular manifestations of MPXV infection in detail. One of the uncommon yet considerable MPXV complications is ocular involvement. These injuries are classified as (1) more frequent and benign lesions and (2) less common and vision-threatening sequels. Conjunctivitis, blepharitis and photophobia are the most uncomplicated reported presentations. Moreover, MPXV can manifest as eye redness, frontal headache, orbital and peri-ocular rashes, lacrimation and ocular discharge, subconjunctival nodules and, less frequently, as keratitis, corneal ulceration, opacification, perforation and blindness. The ocular manifestations have been less frequent and arguably less severe within the current outbreak. Despite the possibility of underestimation, the emerging evidence from observational investigations documented rates of around 1% for ocular involvement in the current outbreak compared to a 9-23% incidence in previous outbreaks in the endemic countries. The history of smallpox immunization is a protective factor against these complications. Despite a lack of definite and established treatment, simple therapies like regular lubrication and prophylactic use of topical antibiotics may be considered for MPXV ocular complications. Timely administration of specific antivirals may also be effective in severe cases. Monkeypox usually has mild to moderate severity and a self-limited course. However, timely recognition and proper management of the disease could reduce the risk of permanent ocular sequelae and disease morbidity.

Risk factors for peripheral hypertrophic subepithelial corneal opacification.

BACKGROUND: To evaluate the phenotype, tear secretion and refractive changes of patients diagnosed with peripheral hypertrophic subepithelial corneal opacification (PHSCO). METHODS: This is a retrospective, interventional case series conducted at the Department of Ophthalmology, University Medical Center of the Johannes Gutenberg University Mainz. Medical records of patients diagnosed with PHSCO were analysed. Sex, age, fluorescein tear film breakup time (FTBUT), Schirmer Test II, iris colour and hair colour were assessed. Objective refraction was evaluated at different time points and, in case of surgery, 1 month and 1 year postoperatively. RESULTS: One hundred ninety-five eyes of 112 patients (78.6% female, 21.4% male; mean age 56.2 ± 14.3) were included. The median FTBUT was 6 sec. (Q1: 4/Q3: 8.75; range 1-20 s) (measured in 70 eyes of 36 patients), the median Schirmer Test II was 8 mm (Q1: 5/ Q3:15; range 1-35 mm). In 83 patients (74.1%) both eyes were involved. In 86 eyes of 64 patients (55.3%) superficial keratectomy was performed. Sphere and cylinder changed significantly 1 month and 1 year postoperative compared to the pre-operative objective refraction, while there was no significant change between 1 month and 1 year postoperatively. CONCLUSION: We found that PHSCO occurs mostly bilaterally in middle-aged women and appears to be associated with decreased tear production and reduced tear film stability.

Mucopolysaccharidosis.

Mucopolysaccharidosis are group of inherited metabolic diseases caused by the absence or malfunctioning of lysosomal enzymes resulting in accumulation of glycosaminoglycans. Over time this accumulation damages cells, tissues, and organs. There are seven types of MPS and 13 subtypes that are associated with multiple organ systems, such as the respiratory, liver, spleen, central nervous systems, arteries, skeletons, eyes, joints, ears, skin, and/or teeth. The various types share some common ocular features that differ in terms of the severity of the affection. Visual loss in MPS patients is varied and can be due to corneal clouding, glaucoma, retinopathy, and optic neuropathy. The primary focus of this review is on changes in the cornea and anterior segment in MPS patients, including clinical and novel investigative modalities, current surgical management, effects of systemic therapy like hematopoietic stem cell transplants (HSCT)and enzyme replacement therapy (ERT), as well as significant research developments.

Staged lensectomy and vitrectomy in the management of stage 5C retinopathy of prematurity with corneal opacification: long-term follow up.

AIM: To verify the feasibility and safety of staged lensectomy and vitrectomy in stage 5C retinopathy of prematurity (ROP) with corneal opacification. METHODS: This was a retrospective, interventional, consecutive case series. Twenty-two eyes of 18 stage 5C ROP patients with corneal opacification were included. Regular combined lensectomy and vitrectomy were not prescribed due to the invisible fundus. Staged lensectomy and posterior vitrectomy were performed. The anatomical and visual outcomes were reviewed at the final follow-up visit. RESULTS: The mean gestational age of ROP patients was 29.3±1.6wk (range: 27-32wk), comprising 8 males and 10 females. The average birth weight was 1363.0±300.0 g. All the eyes had corneal opacity and flat or disappeared anterior chambers pre-operatively. Two eyes had complicated cataract and 7 eyes had retrolental fibroplasia. Six eyes had posterior pupillary synechiae or membranes. Seven (31.8%) eyes had vascularly active retinas. The average interval between two procedures was 6.8±4.6mo (2.5-18.5mo). After surgeries, all the patients had normal anterior chambers. Fourteen eyes had clear corneas. The intraocular pressure of 3 eyes with glaucoma was controlled by medication. Two eyes had ocular phthisis. The retina was reattached in 3 eyes and partially attached in 11 eyes. Visual acuity ranged from no light perception to hand motion. CONCLUSION: Staged lensectomy and vitrectomy are procedures that can halt progression to further complications and preserve some useful eyesight in stage 5C ROP patients with corneal opacification. The earlier the lensectomy is performed, the better the prognosis is.

Mucopolysaccharidosis: A broad review.

Mucopolysaccharidosis (MPS) is a group of genetic disorders with seven types and 13 subgroups which are characterized by an inherent deficiency of the enzymes responsible for the degradation of glycosaminoglycans (GAGs). Defective breakdown of GAG products leads to their widespread accumulation within the lysosomes of various organs involving the eye, central nervous system, skeletal, ocular, nervous, respiratory, cardiac, and the gastrointestinal systems. Clinical spectrum varies from mild systemic and ocular abnormalities with a normal life span to severe phenotype, fatal in the first few months of life. Visual disability due to corneal clouding, retinopathy, and optic nerve involvement causes additional impairment of physical and cognitive functions. Treatment modalities such as bone marrow transplantation and enzyme replacement therapies help in increasing the life span as well as the quality of life of the affected patients. For patients with significant corneal clouding, keratoplasty is the answer. The decision to proceed with keratoplasty is governed by various factors such as the motivation of the patient and his family, other systemic affections and anesthesia concerns. A detailed preoperative counseling should be done regarding the expected visual outcomes in the presence of other ocular comorbidities and the postoperative complication such as graft re-opacification, rejection and glaucoma. Future treatment options such as targeted gene therapy and substrate reduction therapy hold promise to reverse corneal clouding, thereby obviating the need for corneal transplantation. These treatment therapies are still in the experimental stages and human trials are needed to validate their outcomes.

Radiofrequency diathermy as a treatment of lipid keratopathy in a radial keratotomy incision.

Purpose: We report a case of lipid keratopathy in a radial keratotomy incision that was successfully managed with radiofrequency diathermy of the neovascular pedicle responsible for the lipid deposition. Observations: No perioperative or postoperative complications were noted. Following the procedure, the lesion showed significant decrease in lipid deposits and opacification along with disappearance of the neovascular pedicle. Conclusions and importance: Radiofrequency diathermy of neovascular pedicle may represent an effective and safe alternative treatment option for treating lipid keratopathy. This is a first ever report of lipid keratopathy inside a radial keratotomy incision that was successfully managed by radiofrequency diathermy.

Effects of Superficial Keratectomy in Peripheral Hypertrophic Subepithelial Corneal Opacification on Front and Back Corneal Astigmatism.

PURPOSE: To evaluate changes of anterior and posterior corneal astigmatism after superficial keratectomy in peripheral hypertrophic subepithelial corneal opacification (PHSCO). METHODS: Patients with PHSCO, who had received superficial keratectomy with mitomycin C 0.02%, were included in this retrospective study. Scheimpflug imaging of the cornea (Pentacam®, Oculus, Wetzlar, Germany), best-corrected visual acuity (BCVA) and objective refraction were determined preoperatively and 3 months after superficial keratectomy. RESULTS: Fifteen eyes of 15 patients (age: 55 ± 16 years; range: 36-82 years) were included. The mean preoperative BCVA was logMAR 0.4 ± 0.2 and improved to logMAR 0.21 ± 0.3 (p < .01) postoperatively. The median preoperative astigmatism of the anterior corneal surface was 4.67 ± 2.4 D (range: 0.9-13.2 D) and decreased to 1.4 ± 0.4 D (range: 0.8-2.3 D) 3 months after surgery. The median astigmatism of the posterior corneal surface was 0.6 ± 0.5 D (range: 0.1-2.2 D) before surgery and decreased to 0.3 ± 0.2 D (range: 0-0.7 D) 3 months after surgery. CONCLUSION: Superficial keratectomy reduces anterior corneal astigmatism more than posterior corneal astigmatism in patients with PHSCO. Furthermore, a myopic shift and corneal steepening in the peripheral and mid-peripheral cornea was observed after removal of the subepithelial corneal opacification spots.

Atypical presentation of Cat Eye Syndrome in an infant with Peters anomaly and microphthalmia with cyst.

PURPOSE: To describe a unique ocular presentation of Cat Eye Syndrome and review the ocular and systemic findings associated with the syndrome. METHODS: Case report with multimodal imaging. RESULTS: A newborn female presented with a unilateral Peters anomaly with contralateral microphthalmia with cyst. The patient's other systemic findings included a hypoplastic right heart, persistent ductus arteriosus, intrauterine growth retardation, bilateral anotia, preauricular ear pits and skin tags, micrognathia, hypoplastic female genitalia, and unilateral cranial nerve VII palsy. Chromosomal microarray testing showed tetrasomy of chromosome 22 in the q11.1-q11.21 region consistent with Cat Eye Syndrome. The patient ultimately underwent a successful optical iridectomy on one side and orbitotomy with excision of the cystic mass on the other. CONCLUSIONS: The co-occurrence of unilateral Peters anomaly with contralateral microphthalmia with cyst in Cat Eye Syndrome is rare and demonstrative of the syndrome's phenotypic variability. The medical and surgical management of these patients may require a multidisciplinary approach and must be tailored to the individual findings and overall systemic health of the patient.

Corneal Opacification and Spontaneous Recovery following Injection of Healon5 into the Corneal Stroma during Intervention for Postoperative Hypotony.

We report the self-limited nature of corneal opacification after accidental injection of Healon5 into the corneal stroma. A 52-year-old male with a new diagnosis of severe stage, primary open-angle glaucoma underwent successful trabeculectomy OS, which was complicated by ocular hypotony and shallow anterior chamber (AC) on postoperative day 1. Healon5, a hyaluronic acid-containing viscoelastic device, was accidentally introduced into the corneal stroma during attempted injection into the AC. The cornea hydrodissected and opacified, leading to precipitous loss of best-corrected visual acuity (BCVA). The corneal opacification spontaneously resolved over a 7-month period without specific intervention. During this period, the patient also underwent cataract extraction with posterior chamber intraocular lens placement and YAG capsulotomy, after which his BCVA returned to approximately baseline. Though intrastromal injection of sodium hyaluronate-containing material has been reported elsewhere, this complication with Healon5 use specifically has yet to be described in the literature and may occur in any procedure involving Healon5 in the AC. This case report is important, since the precipitous loss of BCVA can be alarming to the ophthalmologist and the patient. The affected patient may be counseled that the opacification should improve with time.

Keratopigmentation: Is it a Miracle or an Adventure?

OBJECTIVES: This study is an analysis of the cosmetic and functional results of patients who underwent keratopigmentation (KTP). METHODS: Sixteen eyes of 16 patients, 7 females (43.75%) and 9 males (56.25%) were included in the study. Intrastromal and superficial manual KTP were performed under general anesthesia. Patients with no light perception or with only light perception but total corneal opacification, prosthetic contact lens intolerance, or unwillingness to use a contact lens were studied. The main outcomes were postoperative patient's satisfaction, cosmetic results, pigment stabilization and surgical complications. A grading system (0-5 points) was used to assess patient satisfaction and the cosmetic results. RESULTS: The mean age of the patients was 30.5±12.06 years (range: 16-53 years). Black pigment was used in 10 patients (62.5%), a brownish color in 5 patients (31.25%) and a greenish, yellow, blue, and black color pigmentation was used for 1 patient (6.25%). The mean follow-up was 29.31±15.45 months (range: 8-52 months). In 2 of 16 patients, mild to moderate pigment loss was seen 12 months after the surgery and superficial KTP was repeated. Minimal pigment loss was seen in 5 patients, but the cosmetic results were satisfactory and no secondary surgical procedure was required. Pigment leakage underneath the conjunctiva was seen in only 1 patient. Otherwise, there were no complications associated with keratopigmentation. The postoperative mean patient satisfaction score was 4.18±0.75 points (range: 3-5 points). CONCLUSION: KTP is a safe surgical procedure that is easy to learn and perform, does not require expensive materials, and avoids more extensive and invasive reconstructive ocular procedures. Corneal KTP may have a great impact on future ophthalmic surgical practice from both therapeutic and cosmetic perspectives.

Successful Treatment of Corneal Opacification with Associated Thickened Epithelium by Simple Peeling: Acquired Corneal Subepithelial Hypertrophy (ACSH).

PURPOSE: To study clinical and histopathological findings of corneal opacification caused by thickened epithelium leading to reduced vision and topographical changes and to evaluate the outcome of its removal. METHODS: Twelve patients (17 eyes) with central, paracentral or peripheral corneal opacification were reviewed to obtain their visual acuity, describe their slit lamp (SL) appearance (depth, extent and density) and document their topographic changes before and after peeling of the epithelium under SL or surgical removal under the microscope. Specimens of six cases were available for histopathological examination and immunohistochemical staining. RESULTS: Most of the eye opacifications were secondary to corneal procedures in 10 [Penetrating keratoplasty (PKP) in 7 for congenital glaucoma, keratoconus or adherent leukoma - usually over graft-host junction -, Photorefractive keratectomy (PRK) in 2 and Phototherapeutic keratectomy in one], chronic inflammation following trachoma or non-specific causes (3), and herpetic scar (1). Three cases were considered to be idiopathic. All cases presented with decreased vision, astigmatism or changes in topography or refraction. Their vision, clinical symptoms and topography improved after treatment. Histopathologically, all six cases shared findings that are similar to what have been described as peripheral hypertrophic subepithelial corneal degeneration (PHSCD) rather than Salzmann's nodular degeneration. None of the cases showed inflammation or subepithelial pannus formation in the excised tissue. However, our cases did not fit into the diagnosis of PHSCD because of the location of the corneal opacification (being peripheral in 41% of the corneas, the presence of underlying primary etiologic factors in 82% of the eyes and the bilateral occurrence in 5 patients. CONCLUSIONS: Meticulous SL examination aided by corneal imaging may accurately diagnose and determine the depth of corneal opacification as a cause for reduced vision. Histopathologically, the removed tissue is similar to PHSCD, but cases differ in their clinical profile. Peeling the thickened epithelial/subepithelial tissue is curative in most patients, improves visual and clinical outcome and avoids unnecessary corneal grafting.

Peripheral hypertrophic subepithelial corneal degeneration: clinical aspects related to in vivo confocal microscopy and optical coherence tomography.

PURPOSE: To report the findings of anterior segment optical coherence tomography (AS-OCT) and in vivo confocal microscopy (IVCM) in two patients with peripheral hypertrophic subepithelial corneal degeneration (PHSD). METHODS: Case series by restrospective chart review and imaging analysis of AS-OCT and IVCM. RESULTS: Slit lamp examination of the two patients revealed a bilateral subepithelial-elevated fibrous tissue of the superior-nasal quadrant, as well as inferior-nasal in one of the patients. Best corrected visual acuity ranged from 20/25 to 20/15. AS-OCT showed continuous, homogenous, well-demarked hyperreflective subepithelial band associated with hyperreflectivity in the anterior stroma. IVCM demonstrated normal epithelial cell morphology and arrangement and a fibrous structure subepithelial and in the anterior stroma. CONCLUSION: AS-OCT and IVCM can facilitate the diagnosis of PHSD and differentiate it from other corneal entities that present peripheral opacifications.

Visualization of corneal vascularization in peripheral hypertrophic subepithelial corneal opacification with OCT angiography.

PURPOSE: The major goal of this study was to test the hypothesis that in patients with peripheral hypertrophic subepithelial corneal opacification (PHSCO), visualization of corneal vessels is better with optical coherence tomography angiography (OCTA) than with conventional slit lamp microphotography. METHODS: Patients with PHSCO were included in this prospective study. The corneal findings were photographed using a slit lamp camera (Haag Streit BM 900® ) and visualized with anterior-segment OCT (Optovue XR Avanti, Fremont, California, USA). Additionally, OCTA with the Angiovue Imaging™ System was performed in the area of PHSCO. RESULTS: Thirty-four eyes of 19 patients (26% male and 74% female) with PHSCO were included in this study. In 21 eyes, vascularization in the area of PHSCO was visualized with the Angiovue-OCT, whereas only 10 eyes presented vessels in slit lamp photographs. CONCLUSION: Optical coherence tomography angiography allows better visualization of corneal neovascularization than slit lamp photography in patients with PHSCO. Corneal opacifications were found predominantly nasally, which was reflected by a local enlargement of corneal thickness.

The effect of haemopoietic stem cell transplantation on the ocular phenotype in mucopolysaccharidosis type I (Hurler).

PURPOSE: To determine whether the ocular phenotype in patients with mucopolysaccharidosis type I (MPSI) Hurler is affected by the efficacy of previous haemopoietic stem cell transplantation (HSCT). DESIGN: A retrospective cohort study of patients with MPSI who had undergone treatment with HSCT. METHODS: Ocular phenotype was documented for each patient and compared to levels of biomarkers representing efficacy of previous transplantation. MAIN OUTCOME MEASURES: Assessment of visual acuity (VA), severity of corneal clouding and the presence of optic neuropathy or retinopathy. Biomarker assessment included dermatan sulphate/chondroitin sulphate (DS/CS) ratio and iduronidase enzyme level. RESULTS: Severe corneal clouding was significantly greater in patients with lower iduronidase levels (p = 0.023) and raised DS/CS ratio (R2  = 0.28 p = 0.043). Better VA was related to a higher iduronidase levels (R2  = 0.15, p = 0.004) and lower DS/CS ratio (R2  = 0.38, p = 0.001). CONCLUSION: Improved ocular phenotypes in MPSI are associated with markers signifying efficacy of prior transplant. Early and effective HSCT may result in a better visual prognosis and reduction in ocular complications for patients with MPSI.

New mutations in GJA8 expand the phenotype to include total sclerocornea.

This project expands the disease spectrum for mutations in GJA8 to include total sclerocornea, rudimentary lenses and microphthalmia, in addition to this gene's previously known role in isolated congenital cataracts. Ophthalmic findings revealed bilateral total sclerocornea in 3 probands, with small abnormal lenses in 2 of the cases, and cataracts and microphthalmia in 1 case. Next-generation sequencing revealed de novo heterozygous mutations affecting the same codon of GJA8 : (c.281G>A; p.(Gly94Glu) and c.280G>C; p.(Gly94Arg)) in 2 of the probands, in addition to the c.151G>A; p.(Asp51Asn) mutation we had previously identified in the third case. In silico analysis predicted all of the mutations to be pathogenic. These cases show that deleterious, heterozygous mutations in GJA8 can lead to a severe ocular phenotype of total sclerocornea, abnormal lenses, and/or cataracts with or without microphthalmia, broadening the phenotype associated with this gene. GJA8 should be included when investigating patients with the severe anterior segment abnormality of total sclerocornea.