BIGH3 mutation in a Bangladeshi family with a variable phenotype of LCDI.

AIMS: To report a Bangladeshi family displaying intrafamilial phenotypic heterogeneity of lattice corneal dystrophy type I (LCDI) and to identify the causative mutation. METHODS: Molecular genetic analysis was performed on DNA extracted from all members of the family. Exons of BIGH3 gene were amplified by polymerase chain reaction. Gene mutation and polymorphisms were identified by heteroduplex and sequence analyses. Segregation of the mutation in the family was confirmed by restriction digestion of amplified gene fragments. RESULTS: A heterozygous C --> T transition at the first nucleotide position of codon 124 of the BIGH3 gene was detected in the three affected members and not in the unaffected members of the family. CONCLUSIONS: This is the first report of BIGH3 gene mutation in a Bangladeshi family with phenotypic heterogeneity. This study confirms that BIGH3 gene screening should be undertaken for proper classification of corneal dystrophy, especially in the absence of histopathological examination.

Effects of lamellar keratotomy on postkeratoplasty astigmatism.

AIM: To determine the changes in postkeratoplasty astigmatism induced by lamellar keratotomy. METHODS: A prospective, non-randomised comparative trial of patients undergoing a hinged lamellar corneal flap for treatment of significant astigmatism after penetrating keratoplasty. Uncorrected visual acuity, best corrected visual acuity, refraction, and corneal topography were assessed at 1 and 3 months after the lamellar keratotomy. RESULTS: 17 eyes in 16 patients (13 M, 3F) were included in the study (mean age 48.2 years; range 20-86 years). Six of 17 eyes (35.3%) changed more than 1 dioptre (D) in spherical equivalent by 3 months. Nine of 17 eyes (52.9%) changed more than 1 D in sphere by 3 months. 12 of 17 eyes (70.6%) changed more than 1 D in refractive cylinder. Seven patients of 15 (46.7%) changed more than 1 D in corneal power as measured topographically. Five of 17 eyes (29.4%) changed in refractive cylinder axis more than 15 degrees and this was similar to the change measured topographically of four of 15 eyes (26.7%). Vector analysis showed 60% of eyes had a surgically induced astigmatism (SIA) vector of more than 1 D, including a net corneal astigmatism decrease of more than 1 D in four eyes and increase of more than 1 D in two eyes at 3 months after surgery. Complications of the lamellar keratotomy included two partial buttonholes and one partial wound dehiscence. CONCLUSIONS: The creation of a lamellar flap alone can have significant effects on the astigmatism following penetrating keratoplasty. LASIK for correction of postkeratoplasty astigmatism may be more accurately performed as a two stage procedure rather than a single stage, after the corneal effects of the lamellar keratotomy have stabilised.

Systemic cyclosporin A in high risk penetrating keratoplasties: a case-control study.

AIM: To examine the efficacy of systemic cyclosporin A (CSA) in preventing rejection and graft failure in high risk keratoplasty (PK). METHODS: A retrospective case-control study with 49 patients in both the CSA group and the control group. The patients receiving CSA were at high risk of graft rejection and failure. Controls were identified from surgical audit books and had high risk characteristics. RESULTS: There was no statistical difference in preoperative risk factors and the use of postoperative topical steroids between the two groups. The median follow up in the CSA group was 22 months and 27 months in the control group. One or more rejection episodes occurred in 18 out of 49 (36.7%) cases in the CSA group and 26 out of 49 (53.1%) in the control group. Graft failure from all causes occurred in 16 (32.7%) CSA patients and 18 (36.7%) control patients. Four (8.2%) of the CSA group compared to eight (16.3%) in the control group failed because of rejection. 22 (44.9%) out of 49 patients in the CSA group had side effects. In five (10.2%) patients, CSA was stopped because of the side effects; eight patients had elevated serum urea and creatinine and four developed hypertension. Minor side effects reported include gum hyperplasia, increased sweating, backache, nausea, feeling unwell, oral candidiasis, cramps, and paraesthesia of the extremities. CONCLUSION: These results suggest that the benefit of CSA over conventional therapy in preventing rejection episodes and subsequent graft failure is only moderate and did not reach statistically significant levels in this study. Considering the high frequency of side effects and the cost of CSA, a randomised control trial may be necessary to determine the true value of CSA in high risk penetrating keratoplasty.

Cyclodiode photocoagulation for refractory glaucoma after penetrating keratoplasty.

OBJECTIVE: This study analyzes the results of intraocular pressure (IOP) reduction by contact diode cycloablation (cyclodiode) in cases of refractory glaucoma after penetrating keratoplasty. DESIGN: Retrospective noncomparative, interventional case series. PARTICIPANTS: Twenty-eight eyes in 28 patients attending the Moorfields Eye Hospital. INTERVENTION: Cyclodiode (40 applications x 1.5 W x 1.5 seconds over 270-300 degrees ) was used to control the IOP in refractory glaucoma after penetrating keratoplasty. MAIN OUTCOME MEASURES: Postoperative IOP, graft status, visual acuity, and number of antiglaucoma medications were recorded after cyclodiode treatment. RESULTS: Cyclodiode resulted in a reduction of IOP from a median of 33 mmHg (interquartile range [28, 40.5]) to a median of 15 mmHg (interquartile range [12, 20.5]). Most patients had a significant lowering in IOP with a median reduction of 16 mmHg (interquartile range [12, 25]; P < 0.0001). IOPs of 6 to 21 mmHg were achieved in 22 patients (79%). Sixteen patients (57%) required more than one treatment with cyclodiode to control the IOP, with three patients (11%) requiring three treatments and two patients (7%) requiring four treatments. Visual acuity improved (> two Snellen lines of acuity) in three patients (11%) and remained the same (+/- one Snellen line) in 17 patients (61%). The mean number of antiglaucoma medications before cycloablation was 2.6 and was 1.8 after treatment (P < 0.001). Of the 19 patients (68%) with originally clear grafts, three grafts (16%) developed opacification. One patient (4%), with a history of nanophthalmos and recurrent uveal effusion, had delayed hypotony (IOP < 6 mmHg) occurring 46 months after the diode treatment. All patients had at least 6 months follow-up. CONCLUSIONS: These patients have often undergone multiple previous complicated ocular interventions and are often not suitable for filtration surgery. Reduction of IOP with maintenance of visual acuity and a good safety profile was achieved in most patients in this study but may require multiple treatments. We propose cyclodiode as an effective treatment for many patients in the management of refractory glaucoma after penetrating keratoplasty.

Assessment of the effect of oral clarithromycin on visual outcome following presumed bacterial endophthalmitis.

PURPOSE: The use of clarithromycin was assessed as a biofilm reducing agent in the management of bacterial endophthalmitis. METHODS: 84 eyes of 83 patients presenting with clinical signs highly suggestive of bacterial endophthalmitis were treated using a standard regimen of intraocular vancomycin, amikacin and systemic steroids, which in addition included oral clarithromycin. Ocular penetration of oral clarithromycin in healthy and inflamed eyes was also assessed. RESULTS: Comparing visual acuities at presentation and 6 months, 66% of patients demonstrated an improvement. Intraocular samples were culture positive in 58% of eyes. As compared to culture positive cases, more culture negative cases achieved a visual acuity of 6/12 or better (p = 0.0047). As compared to patients receiving the standard protocol but without clarithromycin, a greater number of culture negative cases demonstrated an improvement in vision of > or = + 6 Snellen lines (p = 0.023). The ocular penetration of clarithromycin into the anterior chamber of inflamed eyes appears sufficient to allow anti-biofilm activity against bacteria at the basic pH encountered in eyes with endophthalmitis. CONCLUSIONS: The ocular penetration of clarithromycin appears adequate for anti-biofilm activity in inflamed eyes. The beneficial effects of oral clarithromycin on visual outcome has been demonstrated in culture negative eyes with clinical signs highly suggestive of bacterial endophthalmitis. The final visual outcome for culture positive cases remains poor.

Retreatment for significant regression after excimer laser photorefractive keratectomy. A prospective, randomized, masked trial.

PURPOSE: Regression, a gradual partial or complete return to the myopic state, remains a common complication of excimer laser photorefractive keratectomy (PRK) and limits the predictability of refractive outcome, especially in high myopia. An estimated 10% to 20% of patients, therefore, request a repeat PRK procedure. This study was designed to provide patient selection criteria and guidelines for successful retreatment. METHODS: One hundred six patients who had regressed were randomized to 1 of 4 retreatment groups comprising (1) those with minimal haze after their first PRK who received an exact retreatment; (2) those with minimal haze treated with a 50% deliberate overcorrection; (3) those with significant haze (> or = 2+ haze) given an exact retreatment; and (4) those with significant haze who received a 50% overcorrection. A Visx 20/20 laser was used in each case. Mean follow-up after retreatment was 12 months (range, 6-18 months). RESULTS: Deliberate overcorrection (groups 2 and 4) resulted in a statistically significantly better refractive outcome (P = 0.026 at 6 months). Analysis of variance showed that significant haze after the first PRK was the most important predictor of a poor outcome after retreatment, other factors being high original myopia, marked regression, and loss of best-corrected visual acuity. CONCLUSIONS: A retreatment PRK procedure for significant regression will reduce residual myopia significantly in the majority of patients, and a deliberate overcorrection (50%) reduces the chance of further regression. However, patients with high myopia who have regressed beyond approximately -3.50 diopters originally and who show significant anterior stromal haze (> 2+) should be retreated only with great caution, because of the risk of further regression, haze, and loss of visual acuity.

Limbal transplantation.

BACKGROUND: Limbal transplantation is a surgical technique of ocular surface epithelial transplantation advocated for a variety of ocular surface disorders with presumed stem-cell deficiency. Limbal transplantation was performed in 18 patients with ocular surface disease, which included aniridia keratopathy, chronic contact lens-associated epitheliopathy, chemical injury, Stevens-Johnson syndrome, and corneal intraepithelial dysplasia. METHODS: Limbal allograft transplantation was performed in nine eyes with the use of heterologous limbal tissue from cadaveric donor eyes or live relatives, whereas nine eyes underwent conventional limbal autograft transplantation. RESULTS: Limbal allograft transplantation resulted in restoration of a stable ocular surface in seven of nine cases, with early visual rehabilitation and significant reduction in symptoms. At a mean follow-up period of 14.7 months, one patient was noted to have failure of the inferior graft related to postoperative microbial keratitis, whereas one patient had acute rejection episode after early cessation of oral cyclosporine. The mean follow-up period for limbal autografts was 27.1 months. Limbal autograft failure occurred in two patients with limbal autograft transplantation for chronic contact lens-associated epitheliopathy. One contact lens wearer had epithelial dysplasia in the fellow eye at the previous donor site. Subclinical involvement of the fellow eye is suggested as a reason for graft failure and donor eye complications in these eyes. CONCLUSIONS: Although it requires a longer follow-up period, limbal allograft transplantation is a viable procedure for bilateral ocular surface disease and for presumed bilateral disease (viz bilateral exposure to injurious agents) and may be a preferred alternative to limbal autograft transplantation for such patients. The role of immunosuppression is being evaluated.

Linkage of congenital hereditary endothelial dystrophy to chromosome 20.

Congenital heredity endothelial dystrophy (CHED) is a rare autosomal dominant disorder of the cornea. We have performed genetic linkage analysis with microsatellite markers on a seven generation British pedigree. Two-point linkage analysis revealed significant linkage of CHED (lod score >3) with seven marker loci mapping to chromosome 20. The highest observed lod score was 7.20 (theta=0.026) with marker D20S114. Multipoint analysis gave a maximum lod score of 9.34 between D20S48 and D20S471. This 2.7cM region lies within 30 cM region recently assigned to posterior polymorphous dystrophy (PPD). PPD and CHED may therefore be allelic, or alternatively it is possible that more than one gene in this region is responsible for these two corneal dystrophies.

Topical heparin in the treatment of ligneous conjunctivitis.

BACKGROUND: Ligneous conjunctivitis is a rare acute or subacute membranous conjunctivitis of unknown etiology for which no generally accepted form of treatment is available. METHODS: Between 1972 and 1993, 17 patients with ligneous conjunctivitis were treated with excision biopsy, meticulous hemostasis, and immediate, intensive topical treatment with heparin, steroids, and, in 12 patients, alpha-chymotrypsin until all signs of conjunctival inflammation had subsided. RESULTS: On histologic examination, the lesions consisted of subepithelial deposits of fibrin in all patients. Eight patients had no recurrence (mean follow-up, 33.1 months) and in four patients the conjunctivitis was controlled after one repeat excision and topical treatment (mean follow-up, 40.3 months). One patient had three recurrences before responding to treatment (follow-up, 24 months). In four patients, treatment was unsuccessful, although lesion-free intervals were longer than usually seen in this condition (mean, 7.8 months). CONCLUSION: These results suggest that intensive and early use of topical heparin may improve therapy results in ligneous conjunctivitis.

The management of corneal perforations associated with rheumatoid arthritis. An analysis of 32 eyes.

BACKGROUND: Sterile corneal ulceration is a rare complication of rheumatoid arthritis and may lead to corneal perforation. Surgical management for visual restoration frequently is unsuccessful. The authors analyze the factors that may determine the failure of corneal surgery in perforations associated with rheumatoid arthritis. METHOD: The management of 29 patients with rheumatoid arthritis with corneal perforations requiring surgical intervention was reviewed. The corneal lesions were classified either as necrotizing keratitis (n = 20) or as ulcers secondary to surface disease (n = 12), depending on the most evident primary pathology. The outcome of different methods for primary repair (i.e., application of tissue adhesive, lamellar graft, or penetrating keratoplasty) and graft survival in penetrating keratoplasties were analyzed. RESULTS: Fifty-seven corneal procedures were performed in 32 eyes. Primary repair was successful (i.e., no further corneal surgery within 6 months was required) in five eyes (25%) with necrotizing keratitis and in eight eyes (67%) with perforations secondary to surface disease. The application of tissue adhesive, when planned as long-term treatment, was unsuccessful in all five eyes. Immunosuppression significantly improved the survival of first penetrating grafts (42% graft survival after 1 year versus 11% without immunosuppression, P = 0.02). Of 25 graft failures, 20 (80%) were caused by recurrent melts up to 6 months after penetrating keratoplasty. Ocular surface infection was responsible for failure in six of ten grafts after that time. CONCLUSION: Complications of corneal surgery in rheumatoid corneal perforations are frequent. The type of surgical procedure, the predominant pathogenic mechanism, and the perioperative immune status influence the outcome. The control of corneal melting and the prevention of surface infection are critical for graft survival.

Granular corneal dystrophy. Visual results and pattern of recurrence after lamellar or penetrating keratoplasty.

BACKGROUND: Granular corneal dystrophy is a rare indication for corneal transplantation. Both penetrating and lamellar keratoplasty have been recommended, but because granular corneal dystrophy is known to recur within the donor material and multiple grafts may be necessary, the best surgical option has not been clearly established. The cellular cause of the dystrophy is unknown and the authors hypothesized that the rate and pattern of recurrence within lamellar and penetrating grafts might give clues to its etiology. METHODS: The authors compared the visual outcome, rate, and pattern of recurrence after 20 penetrating keratoplasties and 11 lamellar keratoplasties for granular corneal dystrophy. RESULTS: Penetrating keratoplasty and lamellar keratoplasty have a good visual outcome in granular corneal dystrophy. Visual acuities after both procedures were not statistically different. Recurrence of the dystrophy within the graft material was almost universal within 4 years. It first appeared centrally and superficially, occasionally adopting a vortex pattern suggesting epithelial involvement. The recurrence-free interval was independent of size and type of graft performed. CONCLUSION: The authors recommend lamellar keratoplasty as a primary procedure in managing visually disabling granular corneal dystrophy if the deposits are limited to the superficial cornea. This is particularly applicable in younger patients in whom multiple procedures may be necessary over a lifetime due to recurrence of the dystrophy, and the lower morbidity rate associated with lamellar keratoplasty becomes appreciable. Although granular corneal dystrophy generally is classified as a stromal dystrophy, the pattern of recurrence is more consistent with an epithelial or tear-borne abnormality than a disease of the stromal keratocyte.

Acanthamoeba keratitis. The value of early diagnosis.

BACKGROUND: The treatment of Acanthamoeba keratitis has been increasingly successful as diagnoses are made earlier. The authors investigated features of the disease and prognosis in a consecutive series of 15 patients who were treated within 1 month of initial symptoms. METHODS: A database of patients with Acanthamoeba infection presenting between March 1984 and March 1992 was analyzed. The recognition, presenting features, culture methods, results, and treatment of the early cases were reviewed to determine the reasons for a good outcome. RESULTS: Recognition depended on perineural infiltrates (11/15), uveitis (10/15), limbitis (14/15), and infiltrated epithelium; 6 of 15 patients had epithelial defects, but only 3 of 15 had ring infiltrates or ulcers. Epithelial biopsy was culture-positive in 12 of 15 patients. Most (11/15) patients needed only two anti-amebal drugs. One patient only required penetrating keratoplasty for uncontrolled disease. The final visual acuity was at least 6/12 in all patients who had been treated within 1 month of first symptoms, whereas only 17 (53%) of 32 eyes of patients who presented after 1 month achieved a visual acuity of 6/12. CONCLUSIONS: Subtle diagnostic signs, supported by comprehensive microbiologic investigation, justify the immediate instigation of specific antiamebal therapy. Treatment within 1 month of onset results in a lower morbidity and a good visual outcome.

Infective endophthalmitis following vitreoretinal surgery.

Eleven cases of endophthalmitis occurring after vitreoretinal surgery are described. At Moorfields Hospital, London, from 1986 to 1990 the incidence of endophthalmitis after explant surgery with or without drain was 0.19% and after vitrectomy was 0.15%. We conclude that the parity may be due to the intraocular instrumentation of most conventional retinal detachment repair procedures. The best indicator of poor prognosis was speed of onset of symptoms, those with rapid evolution having the worst outcome; 2 of these cases were enucleated. Those presenting at 2-3 days had the best outcome, consistent with infection due to a less virulent organism. Delays in diagnosis were in part due to the posterior location of signs of infection. Potential risk factors amenable to prophylactic strategy were identified in 10 of the 11 patients. Supplementary prophylaxis using ciprofloxacin or imipenem is proposed for cases with an identifiable risk factor. After systemic administration these antibiotics achieve vitreous levels that exceed the MIC90 of the commonest causative pathogens.

Excimer laser photorefractive keratectomy for myopia: 12 month follow-up.

A prospective study of excimer laser photorefractive keratectomy was performed with the aim of correcting a range of myopic errors between -1.00 and -10.00 dioptres. Corneal healing was monitored through the first post-operative year by serial assessments of refraction, contrast sensitivity, corneal haze, pachymetry and keratometry. Eighty-one patients were recruited for the study. At 12 months 81% were within +/- 1.00 dioptre of desired emmetropia and with unaided vision of 6/12. Contrast sensitivity was found by Pelli-Robson assessment to be reduced throughout the 12 months and regression analysis predicted recovery by 2 years. At 12 months, however, only 15% of patients were found to have lost a single line of best corrected Snellen acuity. Predictability of results was found to be greatest for initial errors less than -4.00 dioptres. No serious complications were observed during the follow-up period, but refraction had not stabilised in all cases and patients remain under review.

Conjunctival autografting in the surgical management of pterygium.

In a retrospective survey of 117 operations for primary or recurrent pterygium, conjunctival autografting was compared with both excision without conjunctival closure ('bare sclera excision') and excision with complete conjunctival closure. The probability of corneal recurrence at 36 months after surgery was determined by survival curve analysis. In previously unoperated cases conjunctival autografting (n = 15) resulted in a 14% probability of recurrence, compared with 70% for bare sclera excision (n = 50) and 69% for excision with complete conjunctival closure (n = 20). In previously operated cases conjunctival autografting (n = 17) resulted in a 7% probability of recurrence, compared with 82% for bare sclera excision (n = 15). Hazard ratio analysis confirmed the statistical significance of these results at the 95% confidence level. Conjunctival autografting was more likely to produce an improvement in visual acuity than other forms of surgery.

A review of 72 consecutive cases of Acanthamoeba keratitis, 1984-1992.

A review of consecutive cases of Acanthamoeba keratitis presenting since 1984 was undertaken in order to assess prognostic factors, the success of culture procedures and the outcome of medical and surgical management, with reference to current clinical practice. Seventy-two consecutive cases (77 eyes) of Acanthamoeba keratitis have been managed. Sixty-four patients were contact lens wearers, 28 of these wearing disposable lenses. Superficial corneal involvement and perineural infiltrates were common in those diagnosed less than a month after first symptoms, designated 'early' presentation. Ring infiltrates and ulceration with stromal lysis characterised those presenting at 1-2 months ('intermediate') or after 2 months ('late'); these groups also progressed more frequently to hypopyon, scleritis, glaucoma and cataract formation. Positive corneal cultures were obtained in 10 of 14 (71%) intermediate and 17 of 23 (74%) late cases; early cases underwent epithelial biopsy but formal trephine biopsy was not usually justified (1 of 35 cases) and only 19 of 35 (54%) were tissue-positive. Microbial co-isolates were obtained from 20 corneas. Thirty-four penetrating keratoplasties were performed in 23 eyes, 21 whilst inflamed and 13 when quiet. Of 13 failures in inflamed eyes, 9 were due to recurrence of Acanthamoeba infection. Medical cure is known to have been achieved in 64 of 73 (88%) eyes, 4 of the original 77 having been lost to follow-up abroad. Fifty-eight of 73 eyes (79%) achieved a final visual acuity of 6/12, and of the culture-positive cases, 32 of 46 (70%) achieved 6/12.(ABSTRACT TRUNCATED AT 250 WORDS)

Prognosis for keratoplasty in Acanthamoeba keratitis.

STUDY: Penetrating keratoplasty (PK) was undertaken between 1985-1991 at Moorfields Eye Hospital in 13 eyes (19 PKs) of 11 patients who developed Acanthamoeba keratitis. Infection was ultimately controlled in all cases. Retrospective analysis was undertaken to establish risk factors for PK. Six eyes were quiet and 7 had uncontrolled infection at the time of keratoplasty. The outcome for these was compared. COMPLICATIONS: Complications included cataract in 50% of quiet eyes and 100% of inflamed eyes. Intumescent cataract resulted in glaucoma requiring drainage surgery in 4 eyes. Graft rejection episodes occurred in 50% of quiet eyes, but were treated aggressively and did not cause graft failure. RESULTS: Graft survival was excellent for quiet eyes, but was compromised by recurrent infection in inflamed eyes and 6 patients were regrafted. Survival compared poorly with grafting for active herpetic or bacterial keratitis, indicating that early diagnosis and treatment are essential for adequate control of this disease.

Risk factors for the development of postkeratoplasty glaucoma.

From a database of 1,122 penetrating keratoplasties performed under the care of the surgeons of the Corneal Clinic, Moorfields Eye Hospital (London, U.K.), 153 (14%) were identified as being complicated by postkeratoplasty glaucoma. The relative risk for its development varied with the indication for keratoplasty. Keratoconus had the lowest incidence along with some dystrophies, such as macular or granular dystrophy, and these were taken as the baseline for comparison. Anterior chamber dysgenesis syndromes had the highest risk among the indications for keratoplasty. Combined cataract or lens implant surgery was also found to be a risk factor, with anterior vitrectomy, anterior segment revision, and anterior chamber lens implant removal representing a greater risk than extracapsular extraction and posterior chamber lens implantation. Postkeratoplasty glaucoma was also strongly associated with peripheral anterior synechiae formation seen after keratoplasty.