A randomized, placebo-controlled trial of topical cyclosporin A in steroid-dependent atopic keratoconjunctivitis.

OBJECTIVE: This study aimed to investigate the therapeutic effect of topical cyclosporin A (CsA) 2% in maize oil as a steroid-sparing agent in steroid-dependent atopic keratoconjunctivitis. DESIGN: Prospective, randomized, double-masked, placebo-controlled trial. PARTICIPANTS: Twenty-one patients with steroid-dependent atopic keratoconjunctivitis were studied. INTERVENTION: Patients used either topical CsA or vehicle four times daily for 3 months in addition to their usual therapy, and the clinical response was used to taper or stop topical steroids when possible. MAIN OUTCOME MEASURES: Steroid drop usage per week, ability to cease steroid use, scores for symptoms and clinical signs, drop side effects, and overall subjective rating of trial drop by patients and clinician were measured. RESULTS: Cyclosporin A had a greater steroid-sparing effect than did placebo. Nine of 12 CsA patients ceased steroids compared to 1 of 9 placebo patients (P = 0.01), the final steroid use was lower in the CsA group (2.6 +/- 1.4 vs. 27.7 +/- 17.7, P = 0.005), and the mean reduction in steroid use was greater for CsA (85.5 +/- 14.7 vs. 13.9 +/- 16.0, P = 0.005). Clinical signs and symptom scores were reduced to a greater level for CsA. Serious side effects were lid skin maceration in one patient using CsA and an allergic reaction in one placebo patient. Marked blurring of vision after drop instillation was common in both groups, but intense stinging was more common in CsA patients (9/12 vs. 1/9, P = 0.01), limiting frequency of drop use. The clinician rated the trial drops as good or excellent more frequently for CsA (11/12 vs. 0/9, P < 0.0001). CONCLUSIONS: Topical CsA is an effective and safe steroid-sparing agent in atopic keratoconjunctivitis and, despite difficulties in patient tolerance, also improves symptoms and signs.

Excimer laser superficial keratectomy for proud nebulae in keratoconus.

Contact lens intolerance in keratoconus may be due to the formation of a proud nebula at or near the apex of the cone. Excimer laser superficial keratectomy was performed as an outpatients with proud nebulae as treatment patients with proud nebulae as treatment for their contact lens intolerance. The mean period of contact lens wear before the development of intolerance was 13.4 years (range 2 to 27 years). Following the development of intolerance, three patients abandoned contact lens wear in the affected eye while the remainder experienced a reduction in comfortable wearing time (mean = 3.75 hours; range: 0-14 hours). All patients had good potential Snellen visual acuity with a contact lens of 6/9 (nine eyes) and 6/12 (one eye). The proud nebulae were directly ablated with a 193 nm ArF excimer laser using a 1 mm diameter beam. Between 100-150 pulses were sufficient to ablate the raised area. Patients experienced no pain during the procedure and reported minimal discomfort postoperatively. In all cases flattening of the proud nebulae was achieved. Seven patients were able to resume regular contact lens wear (mean wearing time = 10.17 hours; range 8 to 16 hours). In three patients, resumption of contact lens wear was unsuccessful because of cone steepness. All patients achieved postoperative Snellen visual acuity of 6/12 or better with a contact lens. Four patients experienced a loss of one line in Snellen acuity. The mean follow up period was 8.3 months (range 2 to 17 months). Excimer laser superficial keratectomy is a useful technique for the treatment of contact lens intolerance caused by proud nebulae in patients with keratoconus. Penetrating keratoplasty is thus avoided.

Prognostic factors for the progression of keratoconus.

PURPOSE: The progression of keratoconus to a stage where penetrating keratoplasty (PK) is required for visual rehabilitation has considerable implications for affected patients. To assist with counselling, the authors have attempted to identify which factors measurable early in the course of the disease may indicate the likelihood of subsequent surgery. METHODS: The authors reviewed the records of all patients who attended a single center over a 7-year period for contact lens management of their keratoconus. The influence of clinical variables on the time taken for the worst eye to progress to PK was evaluated by actuarial methods and multivariate analysis. RESULTS: Included in the study were 2723 patients with a mean follow-up for unoperated eyes from the first visit of 4.5 years (range, 3 months to 28 years). Data were available for multivariate analysis in 2363 patients. At the end of the study period, 757 eyes (21.6% of all patients) had been grafted. The number of eyes progressing to PK was independently related to both the maximum and minimum keratometry, a corneal cylinder of more than 1.9 mm, the Snellen acuity, the racial group (P < 0.0001), and the age at presentation (P = 0.0006). Sex, laterality, systemic atopic disease, maternal or paternal age at birth, joint hypermobility, and a family history of keratoconus were not statistically related to outcome. Progression to PK in one eye increased the risk of progression in the contralateral eye (P < 0.0001) and a linear model of disease progression is proposed. CONCLUSIONS: Several clinical variables can be measured in patients at the presentation of keratoconus that influence the probability of a subsequent PK.

Life expectancy in keratoconus.

It is observed that few patients over the age of 60 regularly attend the keratoconus clinic at Moorfields Eye Hospital. The hypothesis that patients with keratoconus have a shorter life expectancy owing to underlying connective tissue related disease was tested. From patient records a sample of 337 keratoconus patients aged at least 40 years by 1991 were identified, of which 279 were living, 13 were deceased, and 45 were untraceable. The mortality rate for keratoconus patients was compared with that of the general population using actuarial English life tables. Results show no significant difference between the general population mortality rate and that of the keratoconus sample even with adjustment for social class. Possible explanations for the non-attendance of older patients are discussed.

Surgery to improve contact lens wear in keratoconus.

Contact lens intolerance in keratoconus may be due to the formation of a proud nebula at or near the apex of the cone that gives rise to contact lens related abrasions. These nebulae do not flatten when contact lens wear is discontinued. We describe a simple technique of superficial keratectomy to remove proud nebulae in which the resulting defect healed quickly under a therapeutic hydrogel lens. In all of the six cases described patients were able to resume contact lens wear within one month of the procedure. One case was lost to follow-up. Of the remaining five (follow-up 3-9 months), all achieved comfortable wearing times of 8 hours or more and visual acuities of 20/40 or better. One patient developed a recurrent epithelial defect that resolved on discontinuing lens wear for one week. Corneal transplantation was thus avoided.

Practical Bayesian analysis of a simple logistic regression: predicting corneal transplants.

The Bayesian analysis of a logistic regression model is described using an example of predicting the need for a corneal transplant in keratoconus. Controversy over the use of subjective prior information in Bayesian methods is avoided by a formulation representing negligible prior information. Simple computational procedures are described, and it is argued that the results are more accurate, clearer and make fuller use of the information contained in the data. Analysis of more complex models is considered. In particular, it is argued that classical methods as implemented in the computer package GLIM can be used as approximations to Bayesian methods, particularly at the initial stage of model selection.

Predictors for likelihood of corneal transplantation in keratoconus.

A group of 70 patients who had attended the Keratoconus Clinic at Moorfields Eye Hospital over a 10-year period were analysed retrospectively. At the end of this period 23 eyes had undergone corneal transplantation. This gave an overall probability of 16%, various information obtained at the initial visit was then analysed for a possible relationship with the probability of needing a transplant within ten years. The only significant relationship found was the initial corneal radius as determined by the back optic radius of the first contact lens. A graph was constructed plotting probability of corneal transplant against each radius at the first visit, which could assist clinicians in advising patients.

Post keratoplasty dimensional and refractive change in contact lens and spectacle corrected cases.

Two groups of patients who had corneal transplantations for keratoconus were analysed retrospectively. One group had been visually corrected with corneal contact lenses and the second group had worn spectacles or used no optical correction. The reduction in post graft corneal astigmatism with time following removal of sutures was examined by the method of regression in groups. The results showed that the reduction in corneal astigmatism was significantly greater in the contact lens wearing group.