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Iris atrophy in patients with newly diagnosed multibacillary leprosy: at diagnosis, during and after completion of multidrug treatment.

AIM: To describe the prevalence and incidence of iris atrophy in patients with multibacillary (MB) leprosy. METHODS AND PATIENTS: Prospective longitudinal cohort study. 301 newly diagnosed patients with MB leprosy were followed up during the 2 years of treatment with multidrug therapy (MDT) and for a further 5 years with biannual ocular examinations. Incidence of iris atrophy was calculated as the number of patients with iris atrophy per person-year (PY) of follow-up among those who did not have iris atrophy at baseline. Stepwise multiple regression confirmed the presence of specific associations of demographic and clinical characteristics (p<0.05) with iris atrophy, detected by univariate analysis. RESULTS: Iris atrophy was present in 6 (2%) patients at enrolment. During MDT, with 445 PYs of follow-up, 9 patients developed iris atrophy (IR 0.02, 95% CI 0.01 to 0.04) that was associated with cataract (HR 15.13, 95% CI 3.71 to 61.79, p<0.001) and corneal opacities (HR 6.83, 95% CI 1.62 to 28.8, p = 0.009). After MDT, with 2005 PYs of follow-up, 60 patients developed iris atrophy (IR 0.03, 95% CI 0.023 to 0.039) that was associated with age (per decade; HR 1.40, 95% CI 1.10 to 1.78, p = 0.006), skin smear positivity (HR 3.50, 95% CI 1.33 to 9.24, p = 0.011), cataract (HR 3.66, 95% CI 1.85 to 7.25, p<0.001), keratic precipitates (HR 2.76, 95% CI 1.02 to 7.47, p = 0.046) and corneal opacity (HR 3.95, 95% CI 1.86 to 8.38, p<0.001). CONCLUSIONS: Iris atrophy continues to develop in 3% of patients with MB leprosy every year after they complete a 2-year course of MDT, and is associated with age, increasing loads of mycobacteria, subclinical inflammation, cataract and corneal opacity.

Adolescent↗

The mouse Cat4 locus maps to chromosome 8 and mutants express lens-corneal adhesion.

Cat4 is the second largest allelism group in the collection of mouse dominant eye mutations recovered in Neuherberg and carriers express anterior polar cataract, central corneal opacity, and lens-corneal adhesions. We have mapped the Cat4 locus of the mouse to central Chromosome (Chr) 8 at position cM 31. Histological characterization of Cat4(a) heterozygotes and homozygotes indicates failure of separation of the lens vesicle from the surface ectoderm. Human anterior segment ocular dysgenesis (ASOD) is autosomal dominant, carriers express an eye phenotype similar to that of Cat4(a) carriers, and it has been mapped to a region of 4q homologous to mouse central Chr 8. Thus, on the basis of phenotype and map position, Cat4 may be a mouse model of human ASOD. The genes Junb, Jund1, Mel, and Zfp42 are discussed as possible candidates for Cat4.

Animals↗

Good visual result following early penetrating keratoplasty for Peters' anomaly.

Visual results following penetrating keratoplasty for congenital corneal opacities have been generally disappointing, prompting many ophthalmologists to recommend no surgery for congenital, monocular corneal opacities. A 14-day-old boy had a penetrating keratoplasty performed for unilateral Peters' anomaly and microcornea. Visual acuity 49 months after surgery was 20/40 and peripheral fusion was present. Early surgery with early suture removal, amblyopia therapy, frequent clinical examinations, and motivated, well-informed parents were important factors in obtaining a good visual result.

Amblyopia↗

Scoring for eye irritation tests.

Scoring of the rabbit eye test and the resulting evaluation and classification should provide useful information about the likelihood that a test material may cause injury on contact with the human eye. When an animal test is necessary, a rabbit eye test based on the following characteristics is proposed for deriving the maximum information from the fewest animals. The ocular effects of interest should include corneal opacity, iritis and conjunctival redness. Animals should be scored for each ocular effect at 24, 48 and 72 hr after the test substance is administered. If an animal is negative at all three scoring times, it can be removed from the test at 72 hr. If it shows a positive effect at a scoring time but the lesion clears at 72 hr, it can be removed at 72 hr. If it shows a positive effect that does not clear at 72 hr, it should be scored again on day 7 when the test ends. However, if an animal shows severe effects at one or more scoring times, it can be removed from the test at 72 hr. An animal is positive if any one of the following criteria is observed at 24, 48 or 72 hr: corneal opacity of 1 or above, iritis of 1 or above, or conjunctival redness of 2 or above. Severe ocular effects (noted at 24, 48 or 72 hr) that may endanger sight deserve special recognition for the classification of chemicals and include corneal opacity of 3 or above, or iritis of 2. This proposal is consistent with the opinions of the majority of respondents who attended the Workshop on Updating Eye Irritation Test Methods, Proposals for Regulatory Consensus. The most notable exception was the suggestion by respondents to add conjunctival chemosis as one of the scoring parameters.

Animals↗

Ocular findings in X-linked ichthyosis: a survey on 38 cases.

The authors report on the occurrence of ocular abnormalities in X-linked ichthyosis (XLI) patients, in their carrier mothers and in healthy volunteers who served as controls. The diagnosis of XLI was based on: (1) demonstration of steroid sulfatase deficiency in cultured skin fibroblasts; (2) lack of hybridization of patient's deoxyribonucleic acid (DNA) with specific steroid sulfatase complementary DNA probe; (3) electrophoretic mobility of plasma lipoproteins. Cholesterol sulfate plasma levels were also determined. The incidence of corneal opacities was the same in XLI patients and in their carrier mothers (23.7 and 24.3%, respectively). Neither other corneal nor ophthalmological alterations were found. Moreover, in XLI patients the plasma levels of cholesterol sulfate were about twenty times higher than in controls. Our findings demonstrate that ocular changes do not seem to be an absolute criterion for a definite diagnosis of XLI and the fact that the pathogenesis of corneal opacities is not due to an accumulation of cholesterol sulfate, but rather that this compound probably induces physicochemical changes of the corneal tissue properties.

Adolescent↗

Pattern of amblyopia and fixation after keratoplasty.

Forty cases of clear corneal grafts in 2 groups of patients who developed corneal opacities either before or after 5 years of age were investigated for the pattern of amblyopia and fixation. A severe irreversible form of amblyopia with eccentric fixation was observed in cases of unilateral corneal opacity when the anomaly occurred before the age of 5 years and corneal grafting was delayed until the second or third decade of life. If the opacity was bilateral, although the onset was before the age of 5 years, the improvement in visual acuity after corneal grafting occurred in the relatively better eye with foveal fixation. Good visual results were seen after corneal grafting when the offending opacity occurred after the age of 5 years. Foveal fixation was also observed in most of these cases. None of the patients who had a squint preoperatively lost their angle of strabismus. Four cases in group B, however, developed an alternating squint postoperatively.

Adolescent↗

Mitomycin C, ceramide, and 5-fluorouracil inhibit corneal haze and apoptosis after PRK.

PURPOSE: To investigate the effects of mitomycin C (MMC), ceramide, and 5-fluororacil (5-FU) on haze after photorefractive keratectomy (PRK) and exposure to ultraviolet B (UVB) radiation. METHODS: The right eyes of 42 New Zealand white rabbits were treated with PRK to correct -10 diopter with a 5-mm optical zone. Sponges soaked in 0.02% MMC, 10 or 40 micromol/L ceramide, or 0.5% 5-FU were applied to the right eyes of 6 rabbits each, and a tarsorrhaphy was performed. Eight weeks after complete healing, topical 0.02% MMC or 0.5% 5-FU was applied twice daily to the right eyes of 6 rabbits that had previously received PRK but no topical medication. The control group of 6 rabbits was treated only with PRK. Three weeks after PRK, all the laser-treated eyes were exposed to 100 mJ/cm UVB radiation. Corneal haze was assessed biomicroscopically every 2 weeks using the Fantes scale. Eyes were enucleated 2, 7, and 13 weeks after PRK, and tissue specimens were stained with hematoxylin and eosin and with Apostain. RESULTS: Corneal haze was observed in all rabbits after PRK and was aggravated by UVB irradiation. When applied immediately after PRK, MMC induced corneal opacity and apoptosis of keratocytes, but, at later times, this reagent significantly suppressed opacity, Apostain-positive keratocytes and reactivation of keratocytes, even after UVB irradiation. In contrast, ceramide and 5-FU suppressed corneal opacity after PRK, but this effect was not sustained after UVB irradiation. CONCLUSIONS: MMC is a potent inhibitor of haze induced by PRK and UVB irradiation. Throughout the process of corneal wound healing, the severity of apoptosis and reactivation of keratocytes was closely correlated with haze formation.

Animals↗

Opacity of bovine cornea in vitro induced by surfactants and industrial chemicals compared with ocular irritancy in vivo.

The ability of 8 surfactants and 5 industrial chemicals to induce bovine corneal opacity in vitro was investigated using a simple specially constructed instrument, the opacitometer. Concentration-effect curves were constructed for each agent. The relative extent to which the agents caused the development of corneal opacity in vitro correlated well with published data on their ocular irritancy in vivo. It is suggested that the measurement of irritant-induced opacity of isolated bovine cornea in vitro may have certain advantages over in vivo irritancy testing as well as over other alternative in vitro techniques and that it may provide the basis for an objective, cost-effective alternative to many current in vivo ocular irritancy tests.

Animals↗

First report of the Australian Corneal Graft Registry.

In the Australian Corneal Graft Registry's first 18 months of operation, May 1985 to November 1986, data supplied by 53 surgeons relating to 322 graft recipients have been entered and analysed with respect to: the most common presenting diseases (primarily keratoconus, bullous keratopathy and corneal opacities), risk factors (especially prior sensitisation to HLA antigens, corneal vascularisation, past or present anterior segment inflammation and history of raised intraocular pressure [IOP]), donor and recipient sex, cause of donor death, storage procedures for donor eyes, operative procedures accompanying the grafts themselves, and preliminary indications of overall graft survival by actuarial analysis. It is hoped that the establishment of this Registry will not only reinforce the use of actuarial graft survival analysis as the method of choice for transplantation surgeons wishing to monitor the survival of their patients and grafts, but will also provide a useful service for the Australian ophthalmic community in general.

Actuarial Analysis↗

Atypical Peters' anomaly associated with partial trisomy 5p.

PURPOSE: We examined a child who had atypical Peters' anomaly and partial trisomy 5p. METHODS: An 11-week-old female infant with multiple developmental malformations and a partial trisomy 5p had bilateral corneal opacities extending from the center of the cornea to the paralimbal region and bilateral iridocorneal adhesions in the areas of the corneal opacities. RESULTS: In addition to association with several other chromosomal disorders, Peters' anomaly may be associated with partial trisomy 5p. CONCLUSIONS: Since partial trisomy 5p can be diagnosed by genetic evaluation, a chromosomal analysis should be performed for children with Peters' anomaly.

Abnormalities, Multiple↗

Effects of cholestanol feeding on corneal dystrophy in mice.

A cholestanol-enriched diet administered for 8 months to BALB/c mice produced in 20% two kinds of corneal opacities resembling calcific band keratopathy and Schnyder's crystalline dystrophy in humans. The concentrations of cholestanol in serum, liver and cornea of the corneal opacity bearing mice were 30-40-times higher than those of normal mice. On the other hand, brain cholestanol level increased only 7-times in the opacity group as compared with that of control group. There was no significant difference in the cholesterol concentrations of serum and several tissues among opacity, non-opacity and the control group. The crystal particles were observed between epithelial basement membrane and superficial stroma by the electron microscopy. Energy dispersive analysis of the particles revealed that the deposits were composed principally of calcium and phosphorus with other crystalline materials, which was presumed to be cholestanol. These results suggest that the cholestanol may deposit in the cornea from elevated serum levels. Deposition of cholestanol in cornea and related area may be a cause of corneal dystrophy in CTX.

Animals↗

Enhancement of SDZ ICT 322-induced cataracts and skin changes in rats following vitamin E- and selenium-deficient diet.

The indole-3-carboxylic acid scopoine ester. SDZ ICT 322, is a selective hydroxytryptamine (5-HT3) antagonist, which after chronic treatment causes posterior subcapsular cataracts and skin changes such as hair loss, hyperaemia, desquamation and hyperkeratosis in rats. The detailed mechanisms underlying these changes are not yet known. In order to evaluate a possible oxidative stress-induced pathomechanism of SDZ ICT 322, the antioxidative defence capacity in rats was modulated by feeding a special vitamin E- and selenium-deficient (VE/SeD) diet. For this purpose 32 male Wistar rats, age 4 weeks, were pretreated for 8 weeks with either a VE/SeD diet or a normal standard diet. Each dietary group was divided into 8 control and 8 SDZ ICT 322-treated animals. SDZ ICT 322 was administered in feed to rats at an adjusted daily dose level of 125 mg/kg for 14 weeks. Plasma levels of SDZ ICT 322 as well as of the N-desmethyl metabolite were similar in rats fed the different diets in weeks 3, 6 and 14. In SDZ ICT 322 treated VE/SeD rats cataracts were observed by week 7, whereas in rats fed normal diet cataracts were first seen in week 14. In the normal dietary group no corneal opacity was found after SDZ ICT 322-treatment; however, a corneal opacity was seen in the deficiency group in parallel with one of the cataract animals in week 7. The incidence and severity of clinical skin signs were greater and their onset was earlier in the deficiency dietary group: onset occurred after 6 weeks compared to 9 weeks on the normal diet. Thiobarbituric acid reactive substances, an indicator mainly of oxidized lipids, were statistically significantly increased in the urine of rats administered SDZ ICT 322 and the VE/SeD diet. Uric acid, which is an endogenous antioxidant was statistically significantly decreased in the urine and plasma of SDZ ICT 322 VE/SeD treated rats. The clinical eye and skin changes occurring early after VE/SeD feeding, the unchanged drug plasma exposure and unchanged drug metabolite formation in combination with the general pro-oxidative activity of the drug suggest an oxidative stress-mediated pathomechanism of SDZ ICT 322 at high dose levels in rats.

Animals↗

Amyloidosis of corneal stroma in patients with trachoma. A clinicopathologic study of 62 cases.

Sixty-two cases of corneal amyloidosis were studied. The median age of the 48 men and 14 women was 66 years. The patients had bilateral, diffuse corneal opacity extending to the limbus and severe visual impairment. The corneal condition was not familial. Advanced stages of trachoma were present in all individuals. Climatic droplet keratopathy (CDK) was also observed clinically in 19 patients. Histopathologically, the Congo red-positive, birefringent and dichroic amyloid deposits in the stroma were similar to that of lattice corneal dystrophy. Bowman's membrane was mostly absent, and peculiar microcystoid degeneration of the stroma was noted. Electron microscopic studies not only confirmed the diagnosis of amyloid but also showed a more diffuse amyloid pattern than did light microscopy. Trachoma is probably the cause of this corneal degeneration with secondary amyloidosis. The environmental conditions associated with CDK may be contributing factors in some cases.

Adult↗

[Phototherapeutic use of excimer laser].

The photorefractive excimer laser is not only able to alter the refractive power of the corneas but also suitable to treat superficial corneal pathologies. Authors performed phototherapeutic keratectomies (PTK) in 80 eyes of 77 patients. The age was on average (+/- S.D.) 49.4 +/- 22.03 years. The follow-up time varied between 3-24 months. All treatments were performed with the Aesculap Meditec MEL 60 ArF excimer laser, working in the 193 nm extreme ultraviolet-C range. Authors conclude that the best postoperative results can be achieved with PTK in cases of recurrent corneal erosions and superficial corneal opacities. Favourable outcome could be expected in treatment of infectious corneal ulcers. In cases of bullous keratopathy the subjective complaints decreased and it was successful to postpone the time of perforating keratoplasty. The PTK is not recommended in case of corneal Bowen disease and recurrent pterygia. A hyperopic shifts was observed in 2 eyes. Besides, the traditional surgical methods the phototherapeutic keratectomy is an important progress in treatment of superficial corneal pathologies. Applying the method, the recurrent erosions healed quicker, in most of the cases the transparency of the cornea could be reestablished in the pupillary area and the need for perforating keratoplasty could be postponed or avoided.

Corneal Diseases↗

Unusual corneal deposit after the topical use of cyclosporine as eyedrops.

PURPOSE: To report a patient who developed bilateral corneal opacities 5 days after the beginning topical cyclosporine. METHODS: Case report. A 45-year-old woman with graft-versus-host disease presented with bilateral corneal deposits. She had been treated with topical physiological saline solution, sodium hyaluronate, ofloxacin, fluorometholone, and oxybuprocaine. Cyclosporine eyedrops were added for persistent corneal epithelial defect bilaterally. Five days after cyclosporine, she complained of visual loss and dense corneal opacities were detected that covered the pupil bilaterally. RESULTS: Deposits were also observed on the punctal plugs, and infrared spectroscopy and X-ray analysis showed that these deposits had properties of cyclosporine. CONCLUSION: Topical cyclosporine, alone or in combination with other eyedrops, may cause severe corneal deposits in patients with disturbance of the corneal epithelial barrier and decreased tear clearance.

Cornea↗

Ocular irritancy responses to various pHs of acids and bases with and without irrigation.

Acids and alkalies were instilled into the eyes of 2 groups of rabbits; the eyes of one group were washed with tap water 30 s after exposure. Damage seen in washed and unwashed eyes was not always related to pH. Some strong acids with greater acidity than pH 2.5 produced opacities while 0.3% hydrochloric acid with a pH of 1.28 produced no ocular damage. Phenol (5%) and acetic acid (5%) with pHs greater than 2.5 produced damage equivalent to or greater than that produced by equal concentrations (w/v) of the mineral acids. All alkalies with pHs ranging from 11.5 to 13.5 produced opacities and other ocular damage of different degrees depending upon the alkali and its concentration. For example, low concentrations of some alkalies in the pH range from 11.3 to 12.8 produced no ocular changes. The duration of the corneal opacities produced by phenol, 1% sodium hydroxide, acetic acid and anhydrous sodium carbonate and the onset of corneal opacity produced by 5% sulfuric acid, the weak acids and 1% sodium hydroxide were reduced as a result of washing the test eyes 30 s after instillation of the test material. These data suggest that acidity and alkalinity of the test material are not the only factors to be considered in relation to a substances' capacity to produce severe ocular injury. The concentration of the test chemical and its period of contact with the eye prior to washing are also important.

Acids↗

Causes of blindness in children in the blind schools of Ethiopia.

A total of 721 children in the six schools for the blind in Ethiopia were studied. In 1988-1989 histories were taken to ascertain the predisposing factors and ophthalmological examinations and records were used to determine the causes of blindness. Ninety-five per cent of those examined had bilateral blindness, 12% did not know how they had become blind and, of those who provided information on how they became blind, 21% knew that they were born blind, 30% implicated measles as being responsible, and 13% implicated 'mitch' which is an Amharic term used to describe a very wide range of nonspecific and vague illnesses of which measles probably constitutes a significant proportion. Seventy per cent of the blindness was due to either corneal opacity or phthisis bulbi. Of those with non-congenital bilateral corneal opacity or phthisis bulbi, 40% were preceded by measles and 17% by mitch. A study of 66 adults in the handicraft and skill-training centres attached to the blind schools indicated that the principal predisposing factors of blindness were mitch (30%), smallpox (15%), cataract (12%), and traditional eye medicine (11%). Seventy percent had corneal scars of phthisis bulbi and 14% cataract.

Adolescent↗

A corneal abnormality associated with trisomy 8 mosaicism syndrome.

Eye abnormalities are a significant feature of trisomy 8 mosaicism syndrome. This paper gives the first account of the specific histopathology of a corneal opacity which is characteristic of this syndrome. The importance of early recognition is stressed because of potential therapeutic visual improvement. The necessity of including mosaic trisomy 8 in the differential diagnosis of such corneal opacities is illustrated by this case.

Chromosomes, Human, Pair 8↗