Keratoprosthesis: preoperative prognostic categories.

PURPOSE: Recent advances aimed at preventing and treating complications after keratoprosthesis surgery have improved prognosis, but it has been suspected that various preoperative diagnoses may carry substantially different postoperative outcomes. This article attempts to clarify the ranking of prognostic categories for patients undergoing keratoprosthesis surgery. METHODS: A retrospective review of the outcome in a recent series of 63 patient eyes operated at the Massachusetts Eye and Ear Infirmary between 1990 and 1997 and followed up for a minimum of 21 months. Anatomic retention of the device and the loss of vision caused by complications were recorded. The patients were divided into four categories according to preoperative cause. RESULTS: Anatomically, one keratoprosthesis extruded spontaneously. Another 10 were permanently removed because of complications. Of the 63 eyes, 10 never achieved a visual acuity of at least 20/200 vision because of preexisting retinal or optic nerve damage. The remaining 53 had a visual acuity of 20/200 to 20/20 as follows: Stevens-Johnson syndrome (n = 7), after 2 years: 33%, after 5 years: 0%; chemical burn (n = 17), after 2 years: 64%, after 5 years: 25%; ocular cicatricial pemphigoid (n = 20), after 2 years: 72%, after 5 years: 43%; graft failure in noncicatrizing conditions (dystrophies, degenerations, or bacterial or viral infections) when a repeat graft was expected to have a poor prognosis (n = 19), after 2 years: 83%, after 5 years: 68%. The difference in outcome between the Stevens-Johnson syndrome outcome group and the graft failure group or the ocular cicatricial pemphigoid group was statistically significant. In the group of 53 eyes, visual acuity was restored to 20/200 to 20/20 for a cumulative total of 138 years. CONCLUSION: Outcome of the keratoprosthesis surgery varied markedly with preoperative diagnosis. Most favorable was graft failures in non-cicatrizing conditions, whereas Stevens-Johnson syndrome was the worst. Ocular cicatricial pemphigoid and chemical burns occupied a middle ground. The difference between the groups seemed to correlate with the degree of past preoperative inflammation.

Secondary glaucoma in patients with uveitis.

PURPOSE: To evaluate the prevalence of secondary glaucoma (SG), clinical forms of uveitis more frequently associated with glaucoma, and describe the treatment and complications encountered in a cohort of patients with glaucoma and uveitis during a 10-year period. METHODS: The hospital records of patients with uveitis referred to the Immunology Service of the Massachusetts Eye and Ear Infirmary for a decade were reviewed for cases of SG. RESULTS: One hundred and twenty of the 1,254 patients (9.6%) with uveitis developed SG. SG was more frequent in anterior uveitis (67%) but was also associated with posterior uveitis (13%) and pars planitis (4%). Herpetic keratouveitis (22%), Fuchs' iridocyclitis (19%), juvenile rheumatoid arthritis-associated iridocyclitis (16%), syphilis (14%), and sarcoidosis (12%) were the leading types of uveitis associated with SG. Despite aggressive medical and surgical therapy, SG was associated with progressive visual field loss and optic nerve damage in 39 patients (33%). CONCLUSION: SG is an underappreciated, vision-threatening complication in patients with uveitis. Increased vigilance for emergence of this complicating problem during the care of patients with uveitis is warranted, and medical and surgical treatment for reducing IOP should be especially aggressive in these patients. We hypothesize that earlier, more aggressive treatment of uveitis will reduce the presence of glaucoma as an additional vision-robbing complication of uveitis.

Outcomes in anterior uveitis associated with the HLA-B27 haplotype.

OBJECTIVE: This study aimed to test the hypothesis that patients presenting with anterior uveitis who are HLA-B27 positive, either with or without associated systemic disease, have a less-favorable outcome than do patients with idiopathic anterior uveitis who are HLA-B27 negative. DESIGN: Retrospective case-controlled series. PARTICIPANTS: Ninety-seven patients who were HLA-B27 positive with no systemic disease, 94 patients who were HLA-B27 positive with systemic disease, and 72 patients who were HLA-B27 negative who presented with anterior uveitis were studied. MAIN OUTCOME MEASURES: Ocular complications (e.g., secondary glaucoma, cataract formation, pupillary synechiae, vitritis, cystoid macular edema, and optic disc edema), medical and surgical treatment, number of recurrent attacks, and final visual acuity were recorded for all patients. RESULTS: The patients who were HLA-B27 positive, either with or without systemic disease, experienced a greater number of complications than did the patients who were HLA-B27 negative. Periocular corticosteroids, systemic corticosteroids, and systemic immunosuppressive chemotherapy were required in a far greater number of HLA-B27-positive patients than in HLA-B27-negative patients (60% vs. 11%, 53% vs. 7%, and 18% vs. 1%, respectively; P < 0.001). The percentage of legally blind eyes was significantly greater in the HLA-B27-positive group, both with and without systemic disease, when compared with the HLA-B27-negative group (11% vs. 2%; P < 0.005). CONCLUSIONS: The prognosis of anterior uveitis associated with the HLA-B27 haplotype, either with or without associated systemic disease, is less favorable when compared with that of HLA-B27-negative patients with idiopathic anterior uveitis.

Long-term follow-up of patients with atopic keratoconjunctivitis.

OBJECTIVE: This study aimed to review the presenting features, treatment administered to, histopathologic findings, and complications encountered in a cohort of patients with atopic keratoconjunctivitis. DESIGN: The study design was a retrospective cohort series. PARTICIPANTS: The medical records of 20 patients with atopic keratoconjunctivitis and a minimum follow-up of 3 years were reviewed. MAIN OUTCOME MEASURES: Conjunctival and corneal complications, visual acuity before and after surgery, and histopathologic features on conjunctival biopsy were measured. RESULTS: Significant keratopathy developed in 70% of patients, corneal neovascularization in 60%, fornix foreshortening in 25%, and symblepharon in 20% during the course of their disease. Eleven patients (12 eyes) required penetrating keratoplasty (3 for tectonic purposes and 8 for visual rehabilitation). Vision improved by four or more lines of Snellen acuity in four eyes, improved by two lines in two eyes, remained the same in five eyes, and worsened by two lines in one eye after keratoplasty. Cataract surgery was performed in seven patients (nine eyes) with vision improving by four or more lines in six patients (eight eyes). CONCLUSION: Atopic keratoconjunctivitis is a potentially blinding disease that may result in a poor visual outcome as a result of corneal complications. Elective surgical intervention may be of benefit and can be considered in those patients whose inflammation is well controlled.

A prospective evaluation of alcohol-assisted versus mechanical epithelial removal before photorefractive keratectomy.

OBJECTIVE: The purpose of the study is to compare alcohol-assisted versus mechanical debridement of the corneal epithelium before photorefractive keratectomy (PRK) for low-to-moderate myopia. DESIGN: A prospective study was performed on a group of consecutive patients operated on at the Massachusetts Eye and Ear Infirmary from February to April 1996 and followed for 6 months. PARTICIPANTS: Eighty patients (eyes) were divided in 2 groups: 40 alcohol and 40 mechanical. INTERVENTION: The patients underwent PRK for myopia (-1.5 to -7.5 diopters) with a Summit Apex excimer laser. The corneal epithelium was removed either with 20% ethanol or with a scalpel blade. MAIN OUTCOME MEASURES: The two groups were compared for epithelial removal time, epithelial defect size at the end of surgery, and rate of re-epithelialization. Uncorrected visual acuity (UCVA), refractive outcome, best-corrected visual acuity (BCVA), and subjective haze were measured at 4 days and at 1, 3, and 6 months. In an additional short-term study, 40 patients (20 alcohol, 20 mechanical) had intraoperative pachymetry performed. RESULTS: Alcohol-assisted de-epithelialization was faster than mechanical debridement (107 [+/-20.6 standard deviation] versus 141 [+/-30.5] seconds [P < 0.0001]) and led to a more circumscribed and reproducible epithelial defect at the end of surgery (87,739 [+/-11,852] versus 103,518 [+/-33,942] square pixels [t test, P = 0.04; f test, P = 0.001]). At 4 days, 95% of the alcohol-treated patients had healed compared with 78% of the mechanically scraped patients (Fisher's exact test, P = 0.04). The alcohol group had a better UCVA at 4 days (logarithm of the minimum angle of resolution UCVA 0.36 [+/-0.22] versus 0.51 [+/-0.26]) and at 1 month (0.14 [+/-0.17] versus 0.22 [+/-0.16] [Mann-Whitney U test, P = 0.02 and P = 0.03]) but equalized at 3 months (0.10 [+/-0.14] versus 0.13 [+/-0.16]) and at 6 months (0.11 [+/-0.15] versus 0.14 [+/-0.13] [Mann-Whitney U test, P = 0.23 and P = 0.34]). There was a trend toward less subjective haze in the alcohol-treated patients over the course of the study (area under the curve, 71.9 [+/-35.3] versus 87.9 [+/-33.8] [Mann-Whitney U test, P = 0.07]). The difference from target was equivalent in both groups at 6 months (-0.22 [+/-0.58] diopter in the alcohol group and -0.43 [+/-0.52] diopter in the mechanical group [t test, P = 0.14; f test, P = 0.57]). There were no differences in intraoperative pachymetry, corneal uniformity index as calculated from the corneal topography, and loss of BCVA between the two groups. CONCLUSIONS: Twenty percent ethanol is a simple, safe, and effective alternative to mechanical scraping before PRK and appears to be associated with a quicker visual rehabilitation.

Primary varicella-zoster keratitis: diagnosis by polymerase chain reaction.

PURPOSE: To report the value of polymerase chain reaction in the diagnosis of a worsening corneal ulcer. METHODS: A 6-year-old boy underwent an emergent penetrating keratoplasty for a corneal ulcer that continued to worsen despite intensive antibiotic therapy. RESULTS: Examination of the corneal specimen by polymerase chain reaction was positive for varicella-zoster virus but negative for herpes simplex. Based on polymerase chain reaction studies, we diagnosed primary varicella-zoster keratitis with corneal perforation. Electron microscopy showed herpetic virus particles in the cornea. CONCLUSIONS: Polymerase chain reaction analysis of corneal buttons at the time of penetrating keratoplasty may benefit patients with undiagnosed recalcitrant corneal ulcers.

Herpes zoster peripheral ulcerative keratitis in patients with the acquired immunodeficiency syndrome.

The purpose of this study was to describe the clinical characteristics and course of peripheral ulcerative keratitis (PUK) secondary to herpes varicella-zoster virus in patients with the acquired immunodeficiency syndrome (AIDS). Three AIDS patients with ocular herpes zoster infection (mean age at onset, 33.0 years; range, 30-42) developed PUK. The three patients had skin involvement, and two of them had bilateral keratouveitis. All were treated with high-dose oral acyclovir (4 g/day) with or without topical antiviral therapy. Two of the patients responded well to oral acyclovir, but one of them stopped the treatment, and bilateral progressive outer retinal necrosis and lethal encephalitis developed. The third patient had a recurrent episode of inflammation with PUK, extensive stromal scarring, and deep neovascularization. AIDS patients with herpes varicella-zoster virus infection may have severe and protracted corneal manifestations, including PUK. The correct diagnosis and aggressive early long-term systemic antiviral treatment must be instituted to control inflammation, ulcer progression, and complications.

HLA typing in patients with ocular manifestations of Stevens-Johnson syndrome.

BACKGROUND: Stevens-Johnson syndrome (SJS) is an acute, self-limited, inflammatory disorder of the skin and mucous membranes. With ocular involvement, SJS has been associated with the class I human leukocyte antigen (HLA)-Bw44. This study examined HLA class II associations in patients with SJS with ocular involvement to help identify possible molecular genetic mechanisms underlying disease susceptibility/resistance. METHODS: Twenty-three white patients with ocular complications secondary to SJS had HLA class II typing performed using polymerase chain reaction-based molecular techniques. Genotype frequency was compared with results obtained from 175 control subjects. RESULTS: HLA-DQB1*0601 was present in four (17%) patients with SJS and in five (3%) control subjects (P < 0.05; relative risk = 7.2). There was no association with HLA-DQB1*0301, which previously has been been strongly associated with recurrent erythema multiforme. None of the class II antigens tested appeared to offer a protective effect against the development of disease. CONCLUSION: HLA-DQB1*0601 was found in a significantly disproportionate number of white patients with SJS and ocular complications. The presence of this allele may confer an increased risk for the development of SJS with ocular complications and provides further evidence for an underlying immunogenetic susceptibility to the development of this disease.

Changing patterns in uveitis of childhood.

BACKGROUND: Although uveitis is relatively uncommon in children, its diagnosis and management present a distinct clinical challenge for the physician. An improved knowledge of disease patterns and associated morbidity will help in the care of children with uveitis. METHODS: The authors reviewed the records of 130 patients with onset of uveitis at 16 years of age or younger. The etiology of uveitis, complications encountered, treatment administered, and visual results were analyzed. RESULTS: Uveitis associated with juvenile rheumatoid arthritis (JRA) was the largest group (41.5%) followed by idiopathic uveitis (21.5%) and pars planitis (15.3%). Twenty-six percent of the eyes had less than 20/200 visual acuity at the time of first referral. Patients with JRA had the highest rate of complications: cataract (71%), glaucoma (30%), band keratopathy (66%), and hypotony (19%). The most frequent complication of pars planitis was maculopathy (55%). Final visual acuity was less than 20/200 in 26% of eyes with JRA, 10.5% with pars planitis, and 14% with idiopathic uveitis. CONCLUSION: Uveitis beginning in childhood is a serious disease associated with sight-threatening complications. Juvenile rheumatoid arthritis-associated uveitis remains a leading cause of ocular morbidity in patients with childhood uveitis. Increased awareness by pediatricians, rheumatologists, and ophthalmologists of the seriousness of ocular complications of uveitis in childhood may lead to earlier diagnosis and more effective treatment regimens in the future.

The value of combined serum angiotensin-converting enzyme and gallium scan in diagnosing ocular sarcoidosis.

PURPOSE: To evaluate the role of combined serum angiotensin-converting enzyme (ACE) activity and whole-body gallium (67GA) scanning in diagnosing sarcoidosis in patients with features consistent with ocular sarcoidosis but with normal or equivocal chest radiographs. METHODS: Serum ACE levels and whole-body 67GA scans were obtained as part of the initial workup in 22 patients with active ocular inflammation and ultimately biopsy-proven sarcoidosis (sarcoid uveitis group). A second group consisting of 70 patients with active uveitis in whom sarcoidosis also was considered a diagnostic possibility also was studied. All 70 patients ultimately had a definitive diagnosis other than sarcoidosis (nonsarcoid uveitis). All patients in this group also had a serum ACE and whole-body 67GA scan performed as part of their initial investigations. RESULTS: All patients in the sarcoid uveitis group had either an elevated ACE level or an abnormal scan. In 16 of the 22 patients, results of both tests were abnormal. In no patient in the nonsarcoid uveitis group were results of both tests abnormal. The sensitivity of an elevated ACE in diagnosing sarcoidosis was 73% and the specificity was 83%. Using the combination of a positive 67GA scan and an elevated ACE, the specificity for diagnosis was 100% and the sensitivity was 73%. CONCLUSIONS: The combination of serum ACE level and whole-body 67GA scan increases the diagnostic specificity without affecting sensitivity in patients with clinically suspicious ocular sarcoidosis who have normal or equivocal chest radiographs.

Analysis of the acute ophthalmic manifestations of the erythema multiforme/Stevens-Johnson syndrome/toxic epidermal necrolysis disease spectrum.

PURPOSE: To evaluate the epidemiology, possible etiologic factors, complications encountered, and treatment administered to a group of patients with ocular involvement in the erythema multiforme/Stevens-Johnson syndrome/toxic epidermal necrolysis disease spectrum who were seen at two large tertiary referral centers over a 34-year period. METHODS: Hospital records from 1960 to 1994 at the Massachusetts General Hospital and Shriners Hospital for Crippled Children were reviewed for patients with erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal necrolysis. Only patients fulfilling specific clinical diagnostic criteria and those who received a diagnosis by a dermatologist were included in the review. RESULTS: A total of 366 patients with erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal necrolysis were identified. Drugs were the most commonly identified etiologic factor in all three conditions: sulfonamides were the most frequently identified agents. Eighty-nine patients (24%) had ocular manifestations at the time of their acute hospital stay. Ocular involvement was seen in 9% of patients with erythema multiforme, in 69% with Stevens-Johnson syndrome, and in 50% with toxic epidermal necrolysis. The ocular problems were more severe in patients with both Stevens-Johnson syndrome and toxic epidermal necrolysis. There was no significant difference between the number of patients who were treated with systemic steroids and those who were not (P = 0.42). CONCLUSIONS: The erythema multiforme/Stevens-Johnson syndrome/toxic epidermal necrolysis disease spectrum remains an important cause of severe visual loss in a significant number of patients. Systemic steroids used during the acute phase of the disease appear to have no effect on the development of ocular manifestations. Studies on the acute immunopathogenic mechanisms occurring in these disease are warranted if more effective therapies are to be found.

Expression of collagens I, III, IV and V mRNA in excimer wounded rat cornea: analysis by semi-quantitative PCR.

A semi-quantitative polymerase chain reaction (PCR) methodology was used to evaluate the kinetic changes occurring in collagens I, III, IV and V mRNA in rat cornea following excimer laser keratectomy. cDNA was synthesized from RNA extracted from rat cornea at various times following excimer laser photoablative keratectomy. Collagen cDNA sequences were subsequently amplified using specific sets of oligonucleotide primers. Competitive PCR amplification was carried out using an internal standard so that a semi-quantitative analysis of message for synthesis of collagen types I, III, IV and V could be performed and time course dynamics of message for these collagens studied. There was a biphasic increase in the levels of collagens III, IV and V mRNA following excimer laser keratectomy. Collagen I mRNA levels demonstrated a more sustained increase and were still elevated at 6 weeks following wounding. Collagens IV and V mRNA showed the largest increase with an approximate three fold increase over controls between 4 days and 1 week. Our results demonstrate that upregulation of stromal collagens I, III, and V mRNA and basement membrane collagen IV mRNA occurs in rat cornea following excimer laser keratectomy.

Increasing the diagnostic yield of conjunctival biopsy in patients with suspected ocular cicatricial pemphigoid.

BACKGROUND: Ocular cicatricial pemphigoid is a chronic, progressive, autoimmune disease that scars mucous membranes and may lead to blindness. It is of critical importance to be able to make the diagnosis as early as possible to allow early treatment. Conjunctival biopsy facilitates the early diagnosis of this condition. MATERIALS AND METHODS: Conjunctival biopsy results of 166 consecutive patients seen over a 7-year period, in whom the diagnosis of ocular cicatricial pemphigoid was considered, were reviewed. RESULTS: One hundred twenty-one patients ultimately received a diagnosis of ocular cicatricial pemphigoid. Immunofluorescence studies demonstrated characteristic deposition of immunoreactants at the epithelial basement membrane zone in 63 patients (sensitivity = 52%). When immunofluorescent-negative or inconclusive biopsies were processed further using an immunoperoxidase technique an additional 37 diagnoses were made. This represented an increase in sensitivity from 52% with immunofluorescence only to 83% with the addition of the immunoperoxidase technique. CONCLUSION: The routine use of the immunoperoxidase technique in immunofluorescent-negative biopsies, allied with appropriate harvesting and handling of biopsied conjunctiva, should significantly increase the diagnostic yield in patients with clinically suspect ocular cicatricial pemphigoid.

Ocular trauma: evaluation with US.

PURPOSE: To examine the value of real-time ultrasonography (US) in the assessment of traumatized eyes with opaque ocular media. MATERIALS AND METHODS: Sixty-one eyes in 60 patients were prospectively examined with US; findings were correlated with findings of clinical and surgical follow-up. Patients with an intraocular foreign body (IOFB) also underwent computed tomography (CT). RESULTS: US demonstrated 56 vitreous hemorrhages, 21 retinal detachments, 12 vitreous detachments, five choroidal detachments, seven IOFBs, three dislocated lenses, and two retrohyaloid hemorrhages. Findings of US and surgery or clinical follow-up were in complete concurrence in 55 cases (90%) and partial concurrence in two cases (3%). US findings were incorrect in four cases (7%). In four cases, US allowed diagnoses that were unsuspected clinically. CONCLUSION: US accurately demonstrates ocular damage and may reveal unsuspected problems. US was superior to CT in demonstration of intraocular damage associated with IOFBs, although CT was superior in determination of the size and site of the IOFB. The presence of dense vitreous traction bands may indicate impending retinal detachment.

Disease relapse in patients with ocular manifestations of Wegener granulomatosis.

PURPOSE: To evaluate possible factors associated with disease relapse in patients with ocular manifestations of Wegener granulomatosis. METHODS: Eight patients with ocular manifestations of Wegener granulomatosis were longitudinally followed for a mean period of 34 months. Serial antineutrophil cytoplasmic antibody (ANCA) levels were determined on all patients. RESULTS: All eight patients had either scleritis alone or scleritis combined with peripheral ulcerative keratitis. Clinical disease remission was achieved in all patients using immunosuppressive chemotherapy. Five patients had subsequent relapse after treatment withdrawal. The serum ANCA level had failed to revert to normal during remission in four of the five patients who had had relapses. The ANCA levels for all three patients who remained in remission without therapy converted to normal. There was no significant difference in the initial serum ANCA level (P = 0.35) or the mean cumulative cyclophosphamide dose (P = 0.13) between those who had a relapse and those who did not. CONCLUSION: Failure of ANCA titers to revert to normal levels may be associated with the potential for relapse in patients with ocular manifestations of Wegener granulomatosis.

Recurrence rate of herpetic uveitis in patients on long-term oral acyclovir.

We examined the recurrence rate of herpetic uveitis (HU) in 13 patients (group A) treated prophylactically with long-term systemic acyclovir (600-800 mg/day) and compared it with that of 7 patients with no prophylactic therapy (group B). HU was diagnosed on the basis of a history of dendritic or disciform keratitis accompanied by iridocyclitis and iris atrophy. The study population consisted of 12 men and 8 women with a mean age at onset of uveitis of 52.9 years (range 19-78 years). All patients were followed for at least 8 months. The mean follow-up time of patients on long-term oral acyclovir was 26.0 months. In this group, only one patient experienced a single recurrent episode of uveitis while on 600-800 mg/day of acyclovir therapy; two additional patients had recurrence of HU within 16.2 months after the acyclovir dose was tapered below 600 mg/day. In striking contrast, 16 recurrences occurred in the 7 patients of group B (p < 0.05). Of these, the initial recurrence occurred within an average of 4.3 months following cessation of therapy. There was a significant difference (p < 0.05) in the mean recurrence-free interval between patients in group A (24.6 months) and those in group B (3.4 months). Herpetic uveitis is a serious ocular disease in which recurrence of inflammation results in severe ocular complications. The long-term use of oral acyclovir may be of benefit in the prevention of recurrences, and hence may reduce the blinding complications of this disease. Efforts at completing a randomized, placebo-controlled trial on this matter by the Herpes Epithelial Disease Study Group were unsuccessful due to insufficient patient recruitment.