Repeat corneal collagen cross-linking after failure of primary cross-linking in keratoconus.

BACKGROUND: Primary corneal collagen cross-linking (CXL) stabilises 96% of progressive keratoconus. There is limited evidence for the treatment of choice when this fails. We present 10 years of repeat CXL and compare with our published experience of primary CXL to (1) identify perioperative risk factors of primary CXL failure and (2) demonstrate the safety and efficacy of repeat CXL. METHODS: Patients undergoing repeat accelerated epithelium-off CXL at St James's University Hospital, Leeds, UK January 2012-August 2022 were identified through electronic patient record, and compared with a previously published cohort of primary CXL patients at the same site. RESULTS: Twenty-one eyes underwent repeat CXL. The mean interval between primary and repeat CXL treatments was 47.1 months (SD 22.5). Twenty (95%) eyes stabilised after repeat CXL at a mean follow-up of 29.9 months. These cases were compared with 151 cases of primary CXL from our previous study. Patients failing primary CXL were significantly younger (21.3 years (SD 7.0) vs 26.7 years (SD 6.5), p=0.0008). Repeat CXL and primary CXL induced a similar amount of flattening of Kmax (-1.2 D (SD 3.9) vs -0.7 D (SD 4.4), p=0.22). A small, but clinically insignificant, improvement in best-corrected visual acuity was found in the repeat CXL group (-0.04 (SD 0.17) vs -0.05 (SD 0.13), p=0.04). No complications of repeat CXL were noted. CONCLUSION: Younger age may be associated with failure of primary CXL. Repeat CXL is an effective and safe treatment for progressive keratoconus despite primary CXL.

Repeated Intracameral Amphotericin B: A Safe Approach for Management of Fungal Anterior Chamber Reactivations After Therapeutic Penetrating Keratoplasty.

PURPOSE: The aim of this study was to describe the safe use of repeated intracameral amphotericin B for anterior chamber reactivations after therapeutic penetrating keratoplasty for Fusarium solani keratitis. METHODS: A 49-year-old woman monthly soft contact lens wearer with a history of overuse and swimming in her lenses presented with a red painful left eye. Her vision was 0.5 logMAR and there was a poorly demarcated corneal infiltrate. Although corneal scrapes and a corneal biopsy were negative, confocal microscopy showed fungal hyphae. After failure of medical treatment, therapeutic penetrating keratoplasty was performed. Fusarium solani sensitive to amphotericin was isolated. There was pan-azole resistance. The patient was managed with topical amphotericin B, and repeated anterior chamber reactivations were managed with intracameral amphotericin B 5 µg in 0.1 mL on 9 occasions over 5 months after sensitivities were known. Topical cyclosporine was used as the sole immunomodulator postoperatively, with no topical steroid use over the 4-year follow-up period. RESULTS: There were no episodes of graft rejection and no endothelial, lenticular, or retinal toxicity. The best-corrected visual acuity is -0.1 logMAR and the endothelial cell count is 2160/mm 2 . CONCLUSION: This report describes the safe and effective use of repeated intracameral amphotericin (cumulative 45 µg) in anterior chamber reactivations after therapeutic penetrating keratoplasty and highlights the role of fungal sensitivity in guiding treatment in refractory cases. It also demonstrated the successful use of topical cyclosporin as the sole postoperative immunomodulatory therapy despite repeated recurrence of infection and consequent increased inflammation in the postoperative period.

Late-onset peripheral ulcerative sclerokeratitis associated with alkali chemical burn.

PURPOSE: To report delayed-onset peripheral ulcerative keratitis (PUK) following alkali injury. DESIGN: Retrospective case series. METHODS: setting: Single institution (Cornea and External Disease Service, Moorfields Eye Hospital). participants: Six eyes of 5 patients with PUK and associated anterior scleritis that had a history of ocular alkali injury. observationprocedure: Patients were identified among PUK patients seen at Moorfields Eye Hospital over a 20-year period. main outcomes measures: Patients' demographics, clinical features, treatment, and outcomes. RESULTS: Recurrent PUK with scleritis following alkali burns occurred in 5 male patients/6 eyes (median age: 22 years, range 18-38) several years after the chemical trauma (average: 6.4 years; range 3-12). Management of PUK in these patients was similar to PUK arising from other etiologies. CONCLUSIONS: In this series of patients there was no evidence of an underlying vasculitic cause for the PUK. A localized autoimmune response may, however, be involved in the pathogenesis of these cases, as seen in an animal model of chemical injury or in late mustard gas keratitis. We hope that this case series will bring this newly described condition to the attention of ophthalmologists and that this may assist in their treatment, which, in this series, required systemic immunosuppressive therapy.

Cataract surgery outcome in eyes with keratoconus.

BACKGROUND: To review the refractive outcome of cataract surgery in eyes with keratoconus. METHODS: We retrospectively reviewed the medical records of 64 consecutive patients (92 eyes) who underwent cataract surgery with implantation of a spherical intraocular lens (IOL). We recorded the method of refractive correction and the effect of the keratometry (K) on the biometry prediction error (BPE). RESULTS: 35 eyes had mild keratoconus (mean K<48 dioptres (D)), 40 had moderate keratoconus (mean K 48 D to 55 D) and 17 had severe keratoconus (mean K>55 D). Actual K values were used in all eyes with mild or moderate keratoconus with a target refraction of approximately -1.0 D in mild keratoconus and -1.5 D in moderate keratoconus that resulted in a mean BPE of 0.0 D and +0.3 D, respectively. The actual K values were used in eight of the 17 eyes with severe keratoconus with a mean target refraction of -5.4 D, which resulted in a mean BPE of +6.8 D. In the remaining nine eyes, a standard K value of 43.25 D was used with a mean target refraction of -1.8 D, which resulted in a mean BPE of +0.6 D. CONCLUSIONS: Using the actual K values with a target of low myopia is a suitable option for spherical IOL selection for eyes with a mean K of ≤55 D. When there is severe keratoconus, the use of actual K values can result in a large hyperopic error and the use of standard K value in these eyes should be considered.

Association of polymorphisms in the hepatocyte growth factor gene promoter with keratoconus.

PURPOSE: Keratoconus is a progressive disorder of the cornea that can lead to severe visual impairment or blindness. Although several genomic regions have been linked to rare familial forms of keratoconus, no genes have yet been definitively identified for common forms of the disease. METHODS: Two genome-wide association scans were undertaken in parallel. The first used pooled DNA from an Australian cohort, followed by typing of top-ranked single-nucleotide polymorphisms (SNPs) in individual DNA samples. The second was conducted in individually genotyped patients, and controls from the USA. Tag SNPs around the hepatocyte growth factor (HGF) gene were typed in three additional replication cohorts. Serum levels of HGF protein in normal individuals were assessed with ELISA and correlated with genotype. RESULTS: The only SNP observed to be associated in both the pooled discovery and primary replication cohort was rs1014091, located upstream of the HGF gene. The nearby SNP rs3735520 was found to be associated in the individually typed discovery cohort (P = 6.1 × 10(-7)). Genotyping of tag SNPs around HGF revealed association at rs3735520 and rs17501108/rs1014091 in four of the five cohorts. Meta-analysis of all five datasets together yielded suggestive P values for rs3735520 (P = 9.9 × 10(-7)) and rs17501108 (P = 9.9 × 10(-5)). In addition, SNP rs3735520 was found to be associated with serum HGF level in normal individuals (P = 0.036). CONCLUSIONS: Taken together, these results implicate genetic variation at the HGF locus with keratoconus susceptibility.

Endothelial cell survival and graft profile analysis in descemet stripping endothelial keratoplasty.

PURPOSE: To report the results of descemet stripping endothelial keratoplasty (DSEK) for a single-surgeon, consecutive case series. METHOD: All patients undergoing DSEK at our institution from 2006 to 2007 under the care of a single consultant ophthalmologist were enrolled. This was a nonrandomized, retrospective case series. Grafts were dissected manually using an artificial anterior chamber and a Morlet lamellar dissector. Data were collected for refractive error, visual acuity, endothelial cell density, graft thickness, and graft profile. RESULTS: Twenty-one eyes of 20 patients were included. The average age at surgery was 69 ± 11 years (range, 37-88 years). The main indication for DSEK was Fuchs endothelial dystrophy. The mean preoperative best spectacle-corrected visual acuity was 1.2 logarithm of the minimum angle of resolution, improving to 0.48 logarithm of the minimum angle of resolution postoperatively (P = 0.001). Endothelial cell density decreased postoperatively compared with preoperatively, but the rate of cell loss decreased over time. No significant correlation was observed between mean graft thickness and final visual acuity or between graft profile and refractive shift. CONCLUSIONS: DSEK is a positive alternative to PK in the treatment of endothelial dysfunction. Visual function improves and the associated refractive change is negligible. Complication rates are low, and graft survival over 2 years is high. Manual preparation of tissue provides grafts of suitable thickness and profile, and endothelial cell density decline is comparable with that of donor's tissue cut via microkeratome or after PK.

Macular dystrophy associated with the Arg172Trp substitution in peripherin/RDS: genotype-phenotype correlation.

PURPOSE: To document the evolution of geographic atrophy in the peripherin/RDS Arg172Trp substitution, provide age-related estimates of visual acuity, and compare with other missense mutations with a similar phenotype (Arg142Trp, Arg172Gln, and Arg195Leu). METHODS: Total area of geographic atrophy in 18 affected individuals with the peripherin/RDS Arg172Trp substitution was measured from retinal photographs and plotted as a function of age. Visual acuity data from these individuals were collated with previously published cases of Arg172Trp substitution to obtain age-related estimates of visual acuity. These were compared with published series with the Arg142Trp, Arg172Gln, and Arg195Leu substitutions, using linear regression. RESULTS: In patients with the Arg172Trp substitution, the increase in total area of chorioretinal atrophy and decline in visual acuity showed significant association with age (R2 = 0.619, P < 0.001; R2 = 0.761, P < 0.001). A trend was observed toward earlier age at onset and worse visual acuity with the Arg172Trp substitution as compared with the Arg142Trp and Arg172Gln substitutions. Linear regression analysis showed that until the age of 60 years, at any given age, visual acuity with the Arg172Trp substitution was significantly worse than the Arg142Trp (P < 0.001) and the Arg172Gln substitutions (P = 0.04). Patients above the age of 60 years were excluded as a floor effect on visual acuity was observed with visual acuity being worse than 6/60 for most patients. CONCLUSION: This paper demonstrates that visual prognosis in macular dystrophies associated with peripherin/RDS may be mutation specific and, for the Arg172Trp substitution, worse than the Arg142Trp and Arg172Gln substitutions.

Diagnostic surprise in an evisceration specimen.

AIMS AND PURPOSE: To report a rare ocular tumor discovered incidentally after evisceration of a painful blind eye. METHODS: Observational case report. RESULTS: A 67-year-old Caucasian lady presented for elective evisceration of chronically irritable phthisical right eye. A history of bilateral retinal detachment surgery 34 years prior followed by phthisis of the right eye was noted. The patient was a smoker but otherwise fit and well. Intra-operatively, the ocular contents were felt to be unusual with hard deeply pigmented lumps being present in the eviscerated tissue. The specimen was sent for histopathology. This was reported as a primary adenocarcinoma of the retinal pigment epithelium after expert histological opinion. The possibilities of a secondary adenocarcinoma with possible primary sites as lung, breast or kidney were ruled out by immuno-histochemical techniques. The patient underwent extensive systemic screening including a whole body CT scan. Exhaustive investigations have not found any other tumor site. CONCLUSION: In the absence of a recognizable source of metastasis, a diagnosis of primary ocular adenocarcinoma has been made with retinal pigment epithelium being the possible site of origin. Literature review shows that primary ocular adenocarcinoma arising from neuroepithelium is a rare but recognized occurrence especially in longstanding blind eyes. This case highlights the importance of routine histopathological examination of eviscerated ocular contents, especially in long standing blind eyes.

Mutations in sodium-borate cotransporter SLC4A11 cause recessive congenital hereditary endothelial dystrophy (CHED2).

Congenital hereditary endothelial dystrophy (CHED) is a heritable, bilateral corneal dystrophy characterized by corneal opacification and nystagmus. We describe seven different mutations in the SLC4A11 gene in ten families with autosomal recessive CHED. Mutations in SLC4A11, which encodes a membrane-bound sodium-borate cotransporter, cause loss of function of the protein either by blocking its membrane targeting or nonsense-mediated decay.

Poststreptococcal syndrome uveitis: a descriptive case series and literature review.

PURPOSE: To describe the clinical features in a series of patients with poststreptococcal uveitis and to review literature on the pathophysiology and management. DESIGN: Retrospective and descriptive case series. PARTICIPANTS: Ten consecutive cases of poststreptococcal syndrome uveitis diagnosed between 1996 and 2003. METHODS: Review of patient case notes. MAIN OUTCOME MEASURES: Age, laterality, clinical features, and anti-streptococcal lysin O titers. RESULTS: Ten consecutive cases of poststreptococcal syndrome uveitis were identified. All our cases had bilateral nongranulomatous inflammation and raised anti-streptococcal lysin O titers. Collating data from previous reports and this series showed that 96% of the patients were below 40 years of age, and 87.5% had evidence of previous streptococcal infection. One third of the patients had posterior segment involvement. In our patients, this was in the form of vitritis, focal retinitis, optic disc swelling, and multifocal choroiditis. CONCLUSIONS: Poststreptococcal syndrome uveitis should be considered in the etiology of acute bilateral nongranulomatous uveitis in children and young patients.

Pharmacological studies on mechanisms of aminophylline-induced seizures in rats.

In the present study, the possible role of free radicals in aminophylline-induced seizures was evaluated in albino rats. Aminophylline (theophylline in ethylene diamine; 50 - 300 mg/kg) induced convulsions in rats in a dose-dependent manner, and both incidence of seizure and mortality were maximum at 300 mg/kg. Conventional anti-epileptics, diphenylhydantoin and dizocilpine, as well as adenosine agonists were ineffective in antagonizing these seizures. On the other hand, phosphodiesterase inhibitors, pentoxyphylline and rolipram, showed insignificant seizurogenic effects. Pretreatment with antioxidants (ascorbic acid, alpha-tocopherol, and melatonin) showed differential attenuating effects on aminophylline seizures and lethality. Further, prior administration of 1-buthionine sulfoxamine (BSO, glutathione depletor) and triethyltetramine (TETA, superoxide dismutase inhibitor), precipitated seizures and enhanced lethality in response to subthreshold doses of aminophylline. The present results suggested of the possible involvement of oxidative stress during aminophylline-induced seizures.

Canaliculitis: the incidence of long-term epiphora following canaliculotomy.

PURPOSE: To review the long-term outcome following surgical treatment for canaliculitis. METHODS: All cases of canaliculitis treated surgically from January 1995 to December 2001 were identified from theatre records. Case notes were reviewed retrospectively looking specifically for delay in diagnosis (defined as two or more visits prior to diagnosis), culture results and outcome following surgical treatment. Telephonic questionnaires were used to assess the incidence of post-treatment epiphora. Symptomatic patients were offered clinic appointments for further assessment and management. RESULTS: Fifteen eyes of 15 patients were identified, 13 were females and 2 males. Mean age was 69.6 years (range 45-87 years). One patient had both upper and lower canaliculitis. The remaining 14 (93.3%) had lower canaliculitis. Diagnosis was delayed in 7 of the 15 patients (46.6%). Culture results were positive in 66.6% with Staphylocococcus spp. being the most common isolate (26.6%). Actinomyces was isolated in only 2 of the 15 cases (13.3%). Conservative treatment had been tried in 5 cases (33.3%). All patients had resolution of symptoms following canaliculotomy. Epiphora was identified in four of the treated eyes on telephonic questionnaires. Of these, three eyes had preexisting lacrimal pathology. Average follow-up was 26 months (range 6-83 months). CONCLUSION: Canaliculotomy is safe and efficacious in the treatment of lacrimal canaliculitis with no demonstrable risk of posttreatment epiphora.