A novel pathogenic variant in LCAT causing FLD. A case report.

BACKGROUND: Fish-eye disease (FED) is due to a partial deficiency in LCAT activity. Nevertheless, Familial lecithin-cholesterol acyltransferase deficiency (FLD), also called Norum disease, appears when the deficiency is complete. They are both rare genetic disorders inherited in an autosomal recessive manner. Clinical signs include decreased circulating HDL cholesterol and dense corneal opacity. Kidney injuries also affect patients suffering from FLD. The diagnosis of FLD is based on the presence of characteristic signs and symptoms and confirmed by genetic testing. CASE PRESENTATION: We present a case of a 63-year-old man showing an altered lipid profile with low HDL cholesterol, chronic kidney disease (CKD) and corneal disorders. He was referred to genetic counseling in order to discard genetic LCAT deficiency due to decreased visual acuity caused by corneal opacity. A massive DNA sequencing was conducted using a multigene panel associated with lipid metabolism disturbances. RESULTS AND GENETIC FINDINGS: Two likely pathogenic variants in LCAT were identified and later confirmed by Sanger sequencing. Both (c.491 G > A and c.496 G > A) were missense variants that originated an amino acid substitution (164Arginine for Histidine and 166Alanine for Threonine, respectively) modifying the protein sequence and its 3D structure. CONCLUSIONS: FLD and FED sharing common biochemical features, and the existence of other diseases with similar clinical profiles underline the need for a timely differential diagnosis aiming to address patients to preventive programs and future available therapies. This case, added to the reduced number of publications previously reported regarding FLD and FED, contributes to better understanding the genetic characteristics, clinical features, and diagnosis of these syndromes.

Clinical Dilemma of Corneal Opacity, Very Low High-density Lipoprotein, and Nephrotic Syndrome: Mystery Revealed.

Lecithin-cholesterol acyltransferase (LCAT) is a liver enzyme necessary for the formation of cholesteryl esters in plasma from free cholesterol. The rare autosomal recessive disease resulting from familial deficiency of this enzyme can lead to nephropathy with kidney involvement generally being the most common cause of death. In addition, the disease process can engender corneal opacity, very low high-density lipoprotein, normochromic anemia, and nephropathy. We present this case of a 35-year-old male who initially visited for a second opinion for renal failure and nephrotic range proteinuria. He underwent renal biopsy which displayed focal segmental glomerulosclerosis-type injury pattern and was started on futile high-dose steroid therapy. A second renal biopsy coincided with the development of corneal opacity leading to a confirmatory testing of LCAT deficiency through biochemistry panel.

Effect of onion extract on corneal haze suppression after air assisted lamellar keratectomy.

This study evaluated the effect of onion extract on corneal haze suppression after applying the air assisted lamellar keratectomy. The air assisted lamellar keratectomy was performed on 24 canine eyes. They were treated with an artificial tear (group C), prednisolone acetate (group P), onion extract (group O) and TGF-ß1 (group T) three times per day from 7 to 28 days after the surgery. Corneal haze occurred on the all eyes and was observed beginning 7 days after the surgery. The haze was significantly decreased in groups P and O from day 14 compared with the group C using the clinical (group P; P=0.021, group O; P=0.037) and objective evaluation method (group P; P=0.021, group O; P=0.039). In contrast, it was significantly increased in group T from day 14 compared with group C based on the clinical (P=0.002) and objective evaluation method (P<0.001). Subsequently, these eyes were enucleated after euthanasia, and immunohistochemistry with α-SMA antibodies was done. The total green intensity for α-SMA was significantly more expressed in group T and significantly less expressed in groups P and O than in group C. Onion extract could have potential as a therapeutic in preventing corneal haze development by suppressing the differentiation of fibroblasts into myofibroblasts.

Efficacy of systemic vitamin C supplementation in reducing corneal opacity resulting from infectious keratitis.

The objective of this study was to determine the effect of vitamin C supplementation on reducing the size of corneal opacity resulting from infectious keratitis.The study included 82 patients (82 affected eyes), admitted for infectious keratitis from January 2009 to August 2013, who were followed for more than 3 months. Patients were divided into control, oral vitamin C (3 g/d), and intravenous vitamin C (20 g/d) groups during hospitalization. Corneal opacity sizes were measured using anterior segment photographs and Image J program (version 1.27; National Institutes of Health, Jinju, South Korea) at admission, discharge, and final follow-up. The corneal opacity size used for analysis was the measured opacity size divided by the size of the whole cornea.The corneal opacity size decreased by 0.03 ± 0.10 in the oral vitamin C group, 0.07 ± 0.22 in the intravenous vitamin C group, and 0.02 ± 0.15 in the control group. Intravenous vitamin C reduced the corneal opacity size more than oral vitamin C (P = 0.043). Intravenous vitamin C produced greater reduction in corneal opacity size in younger patients (P = 0.015) and those with a hypopyon (P = 0.036).Systemic vitamin C supplementation reduced the size of corneal opacity resulting from infectious keratitis. Intravenous vitamin C was more beneficial than oral supplementation, especially in younger patients and those with hypopyon.

Franceschetti hereditary recurrent corneal erosion.

PURPOSE: To describe new affected individuals of Franceschetti's original pedigree of hereditary recurrent erosion and to classify a unique entity called Franceschetti corneal dystrophy. DESIGN: Observational case series. METHODS: Slit-lamp examination of 10 affected individuals was conducted. Biomicroscopic examinations were supplemented by peripheral corneal biopsy in 1 affected patient with corneal haze. Tissue was processed for light and electron microscopy and immunohistochemistry was performed. DNA analysis was carried out in 12 affected and 3 nonaffected family members. RESULTS: All affected individuals suffered from severe ocular pain in the first decade of life, attributable to recurrent corneal erosions. Six adult patients developed bilateral diffuse subepithelial opacifications in the central and paracentral cornea. The remaining 4 affected individuals had clear corneas in the pain-free stage of the disorder. Histologic and immunohistochemical examination of the peripheral cornea in a single patient showed a subepithelial, avascular pannus. There was negative staining with Congo red. DNA analysis excluded mutations in the transforming growth factor beta-induced (TGFBI) gene and in the tumor-associated calcium signal transducer 2 (TACSTD2) gene. CONCLUSION: We have extended the pedigree of Franceschetti corneal dystrophy and elaborated its natural history on the basis of clinical examinations. A distinctive feature is the appearance of subepithelial opacities in adult life, accompanied by a decreased frequency of recurrent erosion attacks. Its clinical features appear to distinguish it from most other forms of dominantly inherited recurrent corneal erosion reported in the literature.

[Corneal opacity in a contact lens wearer on hemodialysis for renal failure]. / Hornhauttrübungen bei einer Kontaktlinsenträgerin mit hämodialysepflichtiger Niereninsuffizienz.

A 53-year-old contact lens wearer on renal dialysis developed visual impairment due to corneal opacity. The opacity was of a crystalline type and diffusely scattered in the anterior cornea. As oxalosis was suspected ascorbic acid was immediately omitted from the dialysis treatment schedule. Within a few weeks the visual acuity recovered and the corneas became nearly clear. The cornea is an uncommon manifestation site for oxalosis. Nevertheless, one should be aware of this possible sign for oxalosis, which can be a life-threatening complication of treatment with high dose ascorbic acid.

The effect of moxifloxacin and gatifloxacin on long-term visual outcomes following photorefractive keratectomy.

PURPOSE: To compare the effect of gatifloxacin and moxifloxacin on visual outcomes after photorefractive keratectomy (PRK). METHODS: Thirty-five PRK patients were treated postoperatively with gatifloxacin (Zymar) in one eye and moxifloxacin (Vigamox) in the fellow eye. Postoperative regimens were otherwise identical. In a previous study (initial phase), we evaluated epithelial healing. In this study (second phase), we compared uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), manifest spherical equivalent (MSE), and corneal haze at 6 months postoperatively for 32 patients using the Wilcoxon signed ranks test. RESULTS: No statistically significant difference was noted between eyes treated with Zymar and Vigamox in terms of UCVA, BSCVA, MSE, or corneal haze at 6 months postoperatively. Two (6%) Vigamox-treated eyes versus 0 (0%) Zymar-treated eyes lost one line of BSCVA from preoperative examination. Median UCVA and MSE were equivalent for both groups. CONCLUSIONS: At 6 months after PRK, there was no significant difference in visual outcomes with either antibiotic.

Evaluation of a topical cyclosporine A prodrug on corneal graft rejection in rats.

PURPOSE: To assess the efficacy of a topical cyclosporine A (CsA), water-soluble prodrug, for promoting the survival of allogenic rat corneal grafts after penetrating keratoplasty (PKP). METHODS: Corneas of Brown-Norway rats (donors) were transplanted to Lewis rats (recipients). Transplanted rats were divided in three treatment groups: group I (PBS) and group II (0.26% Debio088) received drops five times per day. Group III received a daily intramuscular CsA injection (10 mg/kg/day). Blood CsA concentrations were measured on days 2 and 14. On day 4, 10, 13 after PKP, grafts were scored for corneal transparency, edema and extent of neovascularization. An opacity score of greater than or equal to 3 was considered as a nonreversible graft rejection process. On day 14, the experimental eyes were processed for histology. RESULTS: On day 13, 12 of the 18 corneal transplants (67%) in group I showed irreversible graft rejection. Three of 18 transplants (19%) in group II and 5 of 16 transplants (28%) in group III showed irreversible graft rejection (p=0.013/p=0.019, OR=0.14/0.06 versus vehicle). Each mean clinical score for edema, opacity, and neovessels in group II were significantly lower than those of the grafts in group I (respectively p=0.010, p=0.013, p=0.024) and III except for neovessels (respectively p=0.002, p=0.001, p=0.057). Histology confirmed the clinical results. The mean CsA blood levels for groups II and III were, respectively 54+/-141 mug/l and 755+/-319 mug/l on day 2 and 14+/-34 mug/l and 1318+/-463 mug/l on day 14. CONCLUSIONS: Debio088 CsA prodrug drops given five times daily are as effective as intramuscular injection of 10 mg/kg/day for the prevention of acute corneal graft rejection in rats.

Application of energy-dispersive X-ray microanalysis on the diagnosis of atypical calcific band keratopathy.

We describe pathological, ultrastructural, and spectrographic analyses of surgically resected cornea from a man with atypical corneal opacification, and discuss the corneal pathogenesis, and the utility of energy-dispersive X-ray microanalysis (EDXA). The histopathologic features of a case presenting with longstanding bilateral corneal clouding are reported, which was difficult to be diagnosed clinically as calcific band keratopathy. The patient underwent keratoplasty on his right eye. Paraffin sections of the host corneal button were subjected to hematoxylin and eosin (H&E). An adjacent section was studied by means of EDXA. Plastic sections were observed under a transmission electron microscope (TEM). H&E staining revealed flattened corneal epithelial cells and disappearing Bowman's membrane accompanied by numerous basophilic granular deposits within the underlying corneal stroma. EDXA demonstrated the elevated peaks of calcium and phosphorus within the area of granular deposits. TEM revealed electron dense material consistent with extracellular calcospherites. Given the patient's past medical and family history, and the serologic test results, the clinical presentation and histological findings were most consistent with calcific band keratopathy associated with preexisting minimal syphilitic keratitis. Extensive histologic studies including EDXA on resected corneal tissue can be helpful for the differential diagnosis and may elucidate the pathogenesis of corneal diseases.

Ocular cicatricial pemphigoid, keratomycosis, and intravenous immunoglobulin therapy.

PURPOSE: To report the case of a patient developing fungal keratitis in the context of uncontrolled ocular cicatricial pemphigoid (OCP), which, despite intravenous immunoglobulin (IVIg) and other immunomodulatory therapy, progressed to end-stage pemphigoid, with corneal opacification, ankyloblepharon, and xerosis. Keratoprosthesis (KPro) restored functional vision for the patient. METHODS: A 39-year-old man presented with uncontrolled CP and corneal ulcer in the left eye. Conjunctival biopsy diagnosed OCP; corneal scraping and biopsy diagnosed the cause of the corneal ulcer. OCP was treated with systemic steroids, immunosuppressive drugs, and IVIg. Visual rehabilitation was accomplished with Ahmed valve and a type II Dohlman KPro. RESULTS: Immunohistology of the biopsied conjunctiva showed IgG at the epithelial basement membrane zone, confirming the clinical diagnosis of OCP. Microbiologic studies of the corneal biopsy specimen were negative for Acanthamoeba and herpes but positive for Aspergillus niger. The patient's keratomycosis resolved with topical antifungal therapy. Treatment with Dapsone, intravenous-pulse steroid, oral cyclophosphamide, and intravenous immunoglobulin (IVIg) failed to control the OCP, with resultant complete conjunctivization of the cornea. Keratoprosthesis improved the patient's visual acuity from hand movements to 20/20. CONCLUSIONS: Patients with uncontrolled OCP are at increased risk of corneal infection. The difficulty in diagnosing keratomycosis and the relatively rare occurrence of OCP explain the uniqueness of our reported case. OCP may progress to "end-stage" disease despite therapy. Keratoprosthesis can restore vision in selected otherwise seemingly hopeless cases.

Ascorbate prophylaxis for corneal haze after photorefractive keratectomy.

PURPOSE: To evaluate whether prophylactic systemic ascorbic acid influences the average level of haze and the incidence of late onset corneal haze after photorefractive keratectomy (PRK). METHODS: Two consecutive groups of eyes treated with PRK for myopia with or without astigmatism were retrospectively compared. The patients had been treated similarly, with the exception that systemic ascorbate had been supplied orally in one of the groups. Haze intensity was quantified on a scale from 0 (clear cornea) to 4 (anterior chamber not visible). The diagnostic criterion for late onset corneal haze was a haze grade 2 or higher, occurring 4 to 12 months after surgery. RESULTS: One week, 1, 3, 6, and 12 months after surgery, the group without ascorbate (314 eyes) showed haze of average levels 0.61, 0.51, 0.50, 0.32, 0.10, respectively, and the group with ascorbate (201 eyes) showed haze of average levels 0.38, 0.18, 0.16, 0.09, 0.06, respectively. Comparison of the respective values showed a statistically significant difference between the two groups (P<.01) at 1 week, 1, 3, and 6 months. Late onset corneal haze was observed in 11 eyes in the group without ascorbate, and none was observed in the group with ascorbate (P<.02). CONCLUSION: This retrospective nonrandomized clinical study suggests that oral ascorbic acid supplementation may have a prophylactic effect against haze development after PRK. However, routine prophylactic use of ascorbate can be recommended only after a randomized, prospective clinical trial substantiates its efficacy.

Effects of tranilast on cultured rabbit corneal keratocytes and corneal haze after photorefractive keratectomy.

PURPOSE: In vitro and in vivo studies were performed to elucidate the effects of tranilast on cellular proliferation and collagen synthesis. METHODS: Subculturing was carried out using keratocytes from rabbits that underwent photorefractive keratectomy (PRK) and developed corneal haze, and keratocytes from normal rabbit cornea. RESULTS: Tranilast suppressed proliferation in cultured keratocytes from the corneal haze region at doses of 30 and 300 micromol/L and collagen synthesis at doses of 3, 30, and 300 micromol/L. Normal corneal cultures showed suppression of keratocyte proliferation and collagen synthesis only at a high dose of tranilast (300 micromol/L). Betamethasone suppressed proliferation of keratocytes in both haze and normal cornea at a dose of 10 micromol/L, as well as collagen synthesis at respective doses of 1 and 10 micromol/L. Diclofenac sodium suppressed collagen synthesis of keratocytes in haze cornea at a high dose of 100 micromol/L, and in keratocytes in normal cornea, at doses of 10 and 100 micromol/L. In an in vivo study, either 0.5% tranilast, 0.1% betamethasone phosphate eye drops, or a tranilast base solution (control) was instilled four times daily to rabbits that had undergone PRK. Weekly evaluation of the inhibitory effect of these drugs on the development of haze was performed 2 weeks after surgery. Tranilast suppressed haze 6-13 weeks after PRK, but betamethasone phosphate showed no effect. CONCLUSION: These results indicate that tranilast is potentially effective for inhibiting the corneal haze that occurs after PRK.

[The mechanism of cataract formation in persons with beta-thalassemia]. / Mecanismul formarii cataractei la persoane suferind de B-talasemie.

We examined 63 patients with beta-thalassemia whose ages range from 7 to 57 years. Lens opacities were presented in 14 patients--22%. The period these persons had transfusions and were submitted to iron chelating drug--deferoxamine and the concentration of there serum ferritin in the last seven years were noted. Comparing persons with identical ages and transfusion periods we found that patients who were submitted to less chelation therapy patients which started these therapy later and patients with higher values of mean ferritin or with significant picks were in danger to developed cataract. Patients younger of 10 years old didn't developed cataract despite high values of ferritin. All patients after 30 did have lens opacities.

Role of eicosanoids in the ocular response to intracameral hydrogen peroxide.

The intracameral injection of hydrogen peroxide induces a sequence of responses in the tissues bounding the anterior chamber. These changes include intraocular pressure, corneal thickness, iris hyperemia, increased leakiness of the iris vasculature, and edema of the ciliary processes as judged from microscopic examination. Some of these responses appear to include inflammatory effects that may be the result of the local release of eicosanoids. Several antagonists of the arachidonic acid cascade, indomethacin, aspirin, dexamethasone, and nordihydroguaiaretic acid (NDGA) were used to examine their influence on the sequelae of hydrogen peroxide injection. Indomethacin, and high dose (7.5 mg/kg) NDGA were most effective in reducing the number of parameters that were altered after intracameral hydrogen peroxide. Microscopic observations supported the physiological changes and the responses to antagonists. The data indicate that a portion of the ocular tissue responses to intracameral hydrogen peroxide in the rabbit eye may be the result of eicosanoid production in these tissues.

Complications associated with therapeutic soft contact lenses.

The complications of therapeutic hydrophilic contact lens wear are systematically outlined. Hypoxia is the major cause of initial patient failure as well as the long-term problems of corneal edema, neovascularization, and susceptibility to infection. The common difficulties with lens breakage, lens deposits, poor lens retention, and other entities are discussed. Suggestions for avoiding and treating various complications are given, including updated indications and contraindications for fitting these lenses. Careful patient selection and meticulous follow-up are essential.

Vitamin A status of children in Sri Lanka.

A representative country-wide rural nutrition status survey determined the extent and distribution of vitamin A deficiency in Sri Lanka in children 6 through 71 months of age. Trained paramedical personnel recorded the presence or absence of selected ophthalmological signs and symptoms associated with vitamin A deficiency in 13,450 children. The results of the country-wide clinical survey indicate that a vitamin A deficiency problem of public health importance may exist in two of 15 health areas. Serum vitamin A levels were determined on 346 survey children from two of 15 health areas and compared with clinical findings for these areas. The lowest mean serum vitamin A, 26.3 microgram/100 ml, occurred in children with clinical eye findings. A high prevalence of clinical eye findings, 34%, and the low mean serum vitamin A value, 28.2 microgram/100 ml, were found in the group of chronically undernourished children--children who are less than 90% of their expected height for age. The survey results enabled planned redirection of the distribution of vitamin A capsules to preschool children in Sri Lanka to areas shown to have the highest prevalences of ophthalmological signs and symptoms and/or the highest prevalence of chronic undernutrition.

Acute corneal calcification.

This case report describes acute unilateral calcium deposition in the central cornea of a uremic patient with corneal exposure. A mechanism of calcium deposition is discussed. It is suggested that a high calcium-phosphorus product, combined with local factors secondary to injury of the exposed corneal epithelial cells, helped to trigger rapid and dense calcification. Details of the removal technique are presented. Constant irrigation of freshly prepared chelating agent combined with vigorous and frequent massage of residual deposits is necessary to completely remove dense concentrations of calcium.

Effects of an interferon inducer, poly I:C, on acute ocular infection produced by intracameral inoculation of Toxoplasma gondii.

A potent interferon inducer, synthetic polyinosinic acid-polycytidylic acid complex (poly I:C), was used prophylactically and therapeutically in experimental ocular Toxoplasma infections in rabbits. Daily intravenous injections of poly I:C alone or when combined with daily subconjunctival injections of the inducer delayed the appearance of conjunctivitis, corneal opacity, and iritis in Toxoplasma-infected eyes provided that the treatment was started 1 day before the infection. When the treatment was begun at the same time or 1 day after the infection, no delay in the production of the ocular lesions was noted. In no case was the treatment curative or completely suppressive.