Jay H. Krachmer

Keratoconus and related noninflammatory corneal thinning disorders

Keratoconus and other noninflammatory corneal thinning disorders (keratoglobus, pellucid marginal degeneration and posterior keratoconus) are characterized by progressive corneal thinning, protrusion and scarring; the result is distorted and decreased vision. The etiology and pathogenesis of these disorders are unknown but may be associated with a variety of factors, including contact lens wear, eye rubbing, Downs syndrome, atopic disease, connective tissue disease, tapetoretinal degeneration and inheritance. Recent advances in techniques for biochemical and pathological investigation are now allowing further exploration in these areas. Early diagnosis is aided by the finding of irregular corneal astigmatism with inferior corneal steepening. Treatment ranges from simple spectacle correction to keratoplasty. In this review, the past and present literature on corneal thinning disorders is reviewed and practical approaches to diagnosis and management are outlined.

Results of the Prospective Evaluation of Radial Keratotomy (PERK) Study One Year After Surgery

The Prospective Evaluation of Radial Keratotomy (PERK) study is a nine-center, self-controlled clinical trial of a standardized technique of radial keratotomy in 435 patients who had physiologic myopia with a preoperative refraction between -2.00 and -8.00 diopters. The surgical technique consisted of eight incisions using a diamond micrometer knife with blade length determined by intraoperative ultrasonic pachymetry and the diameter of central clear zone determined by preoperative refraction. At one year after surgery, myopia was reduced in all eyes; 60% were within +/- 1.00 diopter of emmetropia; 30% were undercorrected and 10% were overcorrected by more than 1.00 diopter (range of refraction, -4.25 to +3.38 D). Uncorrected visual acuity was 20/40 or better in 78% of eyes. The operation was most effective in eyes with a refraction between -2.00 and -4.25 diopters. Thirteen percent of patients lost one or two Snellen lines of best corrected visual acuity. However, all but three eyes could be corrected to 20/20. Ten percent of patients increased astigmatism more than 1.00 diopter. Disabling glare was not detected with a clinical glare tester, but three patients reduced their driving at night because of glare. Between six months and one year, the refraction changed by greater than 0.50 diopters in 19% of eyes.

Topical cyclosporin A in the treatment of anterior segment inflammatory disease.

Topical cyclosporin A was used in the management of 43 patients with a variety of anterior segment inflammatory disorders that had failed corticosteroid treatment. Treatment with topical cyclosporin A ranged from 1 week to 43 months, with a mean treatment period of 13 months. Thirty-five patients (81%) with disorders including highrisk keratoplasty, atopic and vernal keratoconjunctivitis, ligneous conjunctivitis, ulcerative keratitis, and Moorens ulcer had a beneficial result, with resolution, reduction, or prevention of inflammation. Six patients (14%) with scleritis, ocular cicatricial pemphigoid, or endotheliitis showed no clinical improvement. Two patients (5%) had significant ocular discomfort, and the drug had to be discontinued in them. None of the other patients developed local side effects. Twenty-seven of these patients were followed with serial cyclosporin A blood levels and serum creatinine. None of these patients developed measurable drug blood levels or renal toxicity.

Confocal Microscopy Findings of Acanthamoeba Keratitis

PURPOSE Tandem scanning confocal microscopy was performed on two patients with Acanthamoeba keratitis to provide images detailing characteristic findings of the disease. Although tandem scanning confocal microscopy of Acanthamoeba has been described in previous reports, Acanthamoeba keratitis has not been fully characterized with this instrument. In vivo confocal micrographs showed the double-walled structure of the Acanthamoeba cyst and associated radial keratoneuritis (perineuritis). METHODS We reviewed the records of two patients with a clinical diagnosis of Acanthamoeba keratitis, one with culture-proven Acanthamoeba and the other with a suspected Acanthamoeba infection. Slit-lamp biomicroscopy and in vivo tandem scanning confocal microscopy were performed. The images obtained were compared with images from patients without corneal disease. RESULTS High-contrast round bodies suggestive of Acanthamoeba cysts, as previously described, and irregular forms suggestive of Acanthamoeba trophozoites were found by tandem scanning confocal microscopy. Additionally, we showed conclusively that under certain circumstances (that is, corneal scarring) tandem scanning confocal microscopy can resolve the double-walled structure of the Acanthamoeba ectocyst surrounding the endocyst. Furthermore, radial keratoneuritis was demonstrated, consisting of an irregularly swollen nerve fiber with probable amoebic infiltration. CONCLUSIONS Confocal microscopy can be a useful, noninvasive imaging technique helpful in the study, diagnosis, and treatment of Acanthamoeba keratitis.

The treatment of aqueous-deficient dry eye with removable punctal plugs. A clinical and impression-cytologic study.

Punctal plugs were placed in 18 dry eye patients of the aqueous-deficiency type who were on maximally tolerable medical therapy and who had Schirmer testing with topical anesthetic measuring less than 6 mm. Pretreatment and posttreatment evaluations included rose Bengal and fluorescein staining, Schirmer testing, and conjunctival impression cytology. Six weeks after plug placement, 11 of 18 patients had subjective improvement and were able to decrease dependency on tear supplements; all of these patients have successfully worn plugs for at least 8 months. Although these 11 patients improved clinically, impression cytologic abnormalities persisted 6 weeks after plug placement. Three patients did not improve clinically after punctal plug therapy, and four patients improved subjectively but extruded plugs within 2 weeks of placement. Three of the patients who extruded plugs had marked lid laxity and dilated puncta before placement. Reversible punctal occlusion by plugs may significantly decrease dependency on tear supplements in selected patients.

Paraneoplastic Pemphigus, Cicatricial Conjunctivitis, and Acanthosis Nigncans with Pachydermatoglyphy in a Patient with Bronchogem*c Squamous Cell Carcinoma

A 77-year-old man with chronic conjunctivitis, acanthosis nigricans with pachydermatoglyphy, and pemphigus-like mucocutaneous lesions was found to have a well-differentiated bronchogenic squamous cell carcinoma. Histopathologic and immunofluorescence studies confirmed the diagnosis of paraneoplastic pemphigus. Skin lesions resolved with oral prednisone and azathioprine therapy, but the conjunctivitis and mucous membrane erosions persisted. The conjunctiva later became scarred with foreshortening of the fornices and development of symblepharon. External beam irradiation arrested the growth of the tumor but did not have any effect on the diseased conjunctiva and other mucous membranes. This case demonstrates that cicatrizing conjunctivitis with bullous mucocutaneous lesions may be a clinical sign associated with an occult neoplasm.

Three-year Results of the Prospective Evaluation of Radial Keratotomy (PERK) Study

The Prospective Evaluation of Radial Keratotomy (PERK) study is a nine-center clinical trial of a standardized technique of radial keratotomy in 435 patients who had simple myopia with a preoperative refractive error between -2.00 and -8.00 diopters (D). We report results for one eye of each patient. The surgical technique consisted of eight incisions using a diamond micrometer knife with the blade length determined by intraoperative ultrasonic pachymetry and the diameter of the central clear zone determined by the preoperative refractive error. At three years after surgery, 58% of eyes had refractive error within one diopter of emmetropia; 26% were undercorrected, and 16% were overcorrected by more than one diopter. Uncorrected visual acuity was 20/40 or better in 76% of eyes. The operation was more effective in eyes with a preoperative refractive error between -2.00 and -4.37 diopters. Between one and three years after surgery, the refractive error changed by 1.00 diopter or more in 12% of eyes, indicating a lack of stability in some eyes.

Relaxing Incisions with Augmentation Sutures for the Correction of Postkeratoplasty Astigmatism

We performed a prospective study of relaxing incisions with augmentation sutures in 21 patients who were unable to wear spectacles or contact lenses after penetrating keratoplasty because of high astigmatism. The mean preoperative astigmatism was 9.37 diopters (range, 4.50 to 14.50 diopters), and the mean postoperative astigmatism was 3.73 diopters (range, 0.00 to 7.00 diopters). The net decrease in astigmatism was 6.56 diopters (range, 1.00 to 11.00 diopters), which represents a 67% decrease in astigmatism. The mean vector corrected change in astigmatism was 8.40 diopters (86%). These results were compared with those of our previous study of relaxing incisions without sutures. Overall, there was a significantly greater decrease in astigmatism (67% vs 47%, P = .009) when augmentation sutures were placed 90 degrees away from the relaxing incisions. Furthermore, in patients with more than 8.50 diopters of astigmatism, relaxing incisions with sutures yielded a much greater reduction in astigmatism compared with relaxing incisions without sutures (70% with sutures vs 39% without sutures, P = .002). We recommend relaxing incisions with augmentation sutures as the initial surgical procedure in eyes with more than 8.50 diopters of astigmatism.

THE RESULTS OF PENETRATING KERATOPLASTY FOR PELLUCID MARGINAL CORNEAL DEGENERATION

Over a 14-year period from 1974 to 1988, 12 eyes of 11 patients with pellucid marginal corneal degeneration underwent penetrating keratoplasty. Peripheral corneal thinning required a large eccentric graft in each case. Follow-up ranged from one to eight years (mean, three years). One graft failed because of a persistent epithelial defect with keratolysis of the wound. Although endothelial allograft rejection was common, occurring in seven of 11 (64%) clear grafts, no graft failed because of rejection. Other complications included retinal detachment and a bacterial corneal ulcer. Suture erosion and vascularization of the graft were not problems. Postoperative spectacle correction was dispensed an average of 11 months after surgery. Visual acuity in seven patients without amblyopia, retinal disease, or a previous corneal ulcer at the time of spectacle correction ranged from 20/20 to 20/40 (mean, 20/30). Average final keratometric astigmatism in these patients was 2.46 diopters (range, 0.00 to 5.25 diopters). We believe that penetrating keratoplasty offers an excellent surgical result for patients with pellucid marginal corneal degeneration.

An Immunopathologic Study of Giant Papillary Conjunctivitis Associated with an Ocular Prosthesis

A 21-year-old woman, whose left eye had been enucleated when she was 2 years old, developed giant papillary conjunctivitis and experienced ocular discomfort and increased tearing when she wore her prosthesis. Cultures grew normal flora, and topical antibiotics failed to relieve her symptoms. Immunopathologic studies of a conjunctival biopsy specimen disclosed plasma cells of all five classes of immunoglobulins in the substantia propria and many IgE-containing cells. Russell bodies found in some of the plasma cells were of the IgM and IgG types. The patient was treated with a 2% solution of cromolyn sodium, applied four times a day. Within one month, her symptoms had resolved, there was less conjunctival congestion, and the papillae were much less prominent. Our findings suggested that there may be a heterogenous humoral response in giant papillary conjunctivitis along with a strong immediate (Type I) hypersensitivity component.