David M. Meisler

Dysfunctional Tear Syndrome A Delphi Approach to Treatment Recommendations

Purpose: To develop current treatment recommendations for dry eye disease from consensus of expert advice. Methods: Of 25 preselected international specialists on dry eye, 17 agreed to participate in a modified, 2-round Delphi panel approach. Based on available literature and standards of care, a survey was presented to each panelist. A two-thirds majority was used for consensus building from responses obtained. Treatment algorithms were created. Treatment recommendations for different types and severity levels of dry eye disease were the main outcome. Results: A new term for dry eye disease was proposed: dysfunctional tear syndrome (DTS). Treatment recommendations were based primarily on patient symptoms and signs. Available diagnostic tests were considered of secondary importance in guiding therapy. Development of algorithms was based on the presence or absence of lid margin disease and disturbances of tear distribution and clearance. Disease severity was considered the most important factor for treatment decision-making and was categorized into 4 levels. Severity was assessed on the basis of tear substitute requirements, symptoms of ocular discomfort, and visual disturbance. Clinical signs present in lids, tear film, conjunctiva, and cornea were also used for categorization of severity. Consensus was reached on treatment algorithms for DTS with and without concurrent lid disease. Conclusion: Panelist opinion relied on symptoms and signs (not tests) for selection of treatment strategies. Therapy is chosen to match disease severity and presence versus absence of lid margin disease or tear distribution and clearance disturbances.

Visual acuity, refractive error, and endothelial cell density six months after Descemet stripping and automated endothelial keratoplasty (DSAEK).

Purpose: To evaluate visual acuity, refractive outcomes, and endothelial cell density 6 months after Descemet stripping and automated endothelial keratoplasty (DSAEK). Methods: We performed an institutional review board-approved prospective study of a surgical case series of 34 patients at 2 institutions undergoing DSAEK for Fuchs endothelial dystrophy, pseudophakic bullous keratopathy, or aphakic bullous keratopathy with or without simultaneous phacoemulsification and intraocular lens implantation. Clinical outcomes, including best spectacle-corrected visual acuity (BSCVA), spherical equivalent refraction, and refractive astigmatism and topographic or keratometric astigmatism, were assessed at the 6-month postoperative examination and compared with preoperative values with paired Student t tests. The change in endothelial cell density from the eye bank examination to 6 months after transplantation was similarly evaluated. Results: BSCVA averaged 20/99 preoperatively and 20/42 postoperatively (P < 0.0001). After DSAEK, 30 (88.2%) of 34 patients showed improved BSCVA, and 21 (61.8%) of the 34 patients achieved a BSCVA of 20/40 or better. For patients not undergoing simultaneous phacoemulsification and intraocular lens implantation, a hyperopic shift in refraction of 1.19 ± 1.32 D was noted. Refractive astigmatism, topographic astigmatism, and keratometry showed no statistically significant change. Endothelial cell density of donor corneas averaged 2826 ± 370 cells/mm2, whereas the mean postoperative density was 1396 ± 440 cells/mm2. This finding corresponded to an average loss of 1426 cells/mm2 (50% loss; P = 0.0001). The first half of cases experienced an average cell loss of 1674 cells/mm2 (59% loss) compared with 1181 (41% loss) in the second half of cases (P = 0.005). Three (9%) of 34 grafts experienced iatrogenic graft failure and required reoperation with new donor tissue. Also, 9 (27%) of 34 grafts experienced dislocation in the early postoperative period and required repositioning. Conclusions: In this prospective study of DSAEK for bullous keratopathy and Fuchs endothelial corneal dystrophy, improvement of visual acuity was achieved with only a mild tendency toward hyperopic shift and without significant induced astigmatism. Endothelial cell loss was significant, however, and may be related to surgical experience.

Low-dose Methotrexate Therapy for Ocular Inflammatory Disease

BACKGROUND Methotrexate is a second-line anti-inflammatory agent used in the treatment of rheumatic diseases. At low doses (12.5 mg/week), it is associated with few serious side effects. METHODS Twenty-two patients (5 men, 17 women) with chronic noninfectious ocular inflammatory disease, who had not responded to or who had become intolerant of corticosteroid or alternate cytotoxic agents, were treated weekly with oral low-dose, pulse methotrexate. Treated diseases included chronic uveitis-vitreitis (9), scleritis (4), inflammatory pseudotumor (3), orbital myositis (3), and retinal vasculitis (3). RESULTS Follow-up ranged from 2 to 39 months (mean, 11 months). Response time ranged from 3 to 9 weeks (mean, 5 weeks) after implementation of methotrexate therapy. Sixteen of 22 patients had reduction of inflammatory activity. Fourteen of these 16 patients were able to taper or discontinue corticosteroid therapy. Five patients had complete remission of their disease; six patients did not respond to methotrexate. CONCLUSION Treatment with low-dose methotrexate appears to be effective therapy for steroid-resistant ocular inflammatory disease.

Chronic Propionibacterium Endophthalmitis After Extracapsular Cataract Extraction and Intraocular Lens Implantation

We studied six cases of chronic, indolent intraocular inflammation that occurred after extracapsular cataract extraction and posterior chamber intraocular lens implantation. The inflammation was characterized by a delayed onset, and in three cases had the clinical appearance of a granulomatous iridocyclitis. Cultures of intraocular specimens obtained from six eyes yielded Propionibacterium; five yielded P. acnes. Pleomorphic gram-positive bacilli consistent with Propionibacterium were identified in cytologic or histopathologic studies in four of the six culture-positive cases. After surgical and medical therapy, the inflammation resolved. Postoperative Propionibacterium endophthalmitis may masquerade as a chronic iridocyclitis.

Ocular TRUST: Nationwide Antimicrobial Susceptibility Patterns in Ocular Isolates

PURPOSE Ocular Tracking Resistance in U.S. Today (TRUST) annually evaluates in vitro antimicrobial susceptibility of Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae to ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin, penicillin, azithromycin, tobramycin, trimethoprim, and polymyxin B in national samples of ocular isolates. DESIGN Laboratory investigation. METHODS Prospectively collected ocular isolates (197 S. aureus, 49 S. pneumoniae, and 32 H. influenzae) from 35 institutions and archived ocular isolates (760 S. pneumoniae and 356 H. influenzae) from 34 institutions were tested by an independent, central laboratory. Mean minimum inhibitory concentrations that would inhibit growth of 90% of the tested isolates (MIC(90)) were interpreted as susceptible, intermediate, or resistant according to standardized breakpoints for systemic treatment. S. aureus isolates were classified as methicillin susceptible (MSSA) or methicillin resistant (MRSA). RESULTS MSSA or MRSA susceptibility patterns were virtually identical for the fluoroquinolones, that is, MSSA susceptibility was 79.9% to 81.1% and MRSA susceptibility was 15.2%. Trimethoprim was the only agent tested with high activity against MRSA. All S. pneumoniae isolates were susceptible to gatifloxacin, levofloxacin, and moxifloxacin; 89.8% were susceptible to ciprofloxacin. H. influenzae isolates were 100% susceptible to all tested agents but trimethoprim. Ocular TRUST 1 data were consistent with the eight-year longitudinal sample of archived ocular isolates. CONCLUSIONS The fluoroquinolones were consistently active in MSSA, S. pneumoniae, and H. influenzae. After more than a decade of intensive ciprofloxacin and levofloxacin use as systemic therapy, 100% of ocular S. pneumoniae isolates were susceptible to gatifloxacin, levofloxacin, and moxifloxacin; nonsusceptibility to ciprofloxacin was less than 15%. High-level in vitro MRSA resistance suggests the need to consider alternative therapy to fluoroquinolones when MRSA is a likely pathogen.

Mitomycin C treatment for conjunctival-corneal intraepithelial neoplasia: a multicenter experience.

OBJECTIVE The purpose of the study is to evaluate the efficacy and risks of topical mitomycin C (MMC) for conjunctival-corneal intraepithelial neoplasia (CCIN). DESIGN The study design was a clinical case series of CCIN. PARTICIPANTS Seventeen patients, 16 with biopsy-confirmed CCIN and 1 with invasive squamous cell carcinoma (SCC), were included in the study. INTERVENTION Patients received topical drops of MMC 0.02% to 0.04% four times daily from 7 to 28 days. Retreatment was done in cases of lesion recurrence. MAIN OUTCOME MEASURES The size of the CCIN before and after the treatment and ocular complications post-MMC application were evaluated. RESULTS Ten patients remained disease-free after one course of MMC application. In one case, residual CCIN remained very small without regrowth. In the one patient with invasive SCC and in five patients with CCIN, regrowth occurred within 6 months of the first treatment. After retreatment, invasive SCC and CCIN in an additional two patients were eradicated. In two cases, although the size of the lesions decreased after two and three applications of MMC, regrowth occurred, and the CCIN returned to its original size. In the final case, limited recurrence has occurred and no retreatment has been done. The complications of MMC use included mild-to-moderate conjunctival hyperemia and mild allergy, which resolved after discontinuation of the treatment. Severe pain manifested when treatment was longer than 14 days. CONCLUSIONS Application of topical MMC is an efficient treatment for most but not all cases of CCIN.

Phacoemulsification cataract extraction and posterior chamber lens implantation in patients with uveitis

PURPOSE This study reports outcomes of phacoemulsification cataract extraction and posterior chamber intraocular lens implantation within the capsular bag in patients with uveitis. METHODS We retrospectively reviewed the charts of 32 patients (39 eyes) with uveitis who underwent phacoemulsification cataract extraction and posterior chamber intraocular lens implantation by two surgeons at The Cleveland Clinic Foundation from January 1990 to June 1998. Patients with less than 3 months of follow-up were excluded. RESULTS Diagnoses of uveitis included idiopathic (15 eyes), sarcoidosis (10 eyes), pars planitis (four eyes), CMV retinitis (two eyes), Fuchs heterochromic iridocyclitis (two eyes), syphilis (two eyes), and one eye each of tuberculosis, Crohns disease, HLA-B27 associated, and acute retinal necrosis. Average follow-up was 20 months (range, 3 to 63 months). Best-corrected visual acuity improved in 37 eyes (95%). Average improvement was 4 +/- 3 Snellen acuity lines (range, 1 to 10 lines). Thirty-four eyes (87%) attained final visual acuity better than or equal to 20/40. Visual loss occurred in one eye (3%) with CMV retinitis. No improvement in visual acuity was seen in one eye (3%) that developed a retinal pigment epithelial detachment. Posterior capsule opacification occurred in 24 eyes (62%), 12 of which required Nd:YAG capsulotomy (31%). Other postoperative complications included recurrence of uveitis (41%), cystoid macular edema (33%), epiretinal membrane formation (15%), and posterior synechiae (8%). CONCLUSIONS Phacoemulsification cataract extraction with posterior chamber intraocular lens implantation is safe in patients with uveitis. The incidences of recurrence of uveitis, cystoid macular edema, epiretinal membrane, and posterior synechiae were lower than those reported previously for extracapsular cataract extraction.

Keratoconus Diagnosis with Optical Coherence Tomography Pachymetry Mapping

OBJECTIVE To detect abnormal corneal thinning in keratoconus using pachymetry maps measured by high-speed anterior segment optical coherence tomography (OCT). DESIGN Cross-sectional observational study. PARTICIPANTS Thirty-seven keratoconic eyes from 21 subjects and 36 eyes from 18 normal subjects. METHODS The OCT system operated at a 1.3 microm wavelength with a scan rate of 2000 axial scans per second. A pachymetry scan pattern (8 radials, 128 axial scans each; 10 mm diameter) centered at the corneal vertex was used to map the corneal thickness. The pachymetry map was divided into zones by octants and annular rings. Five pachymetric parameters were calculated from the region inside the 5 mm diameter: minimum, minimum-median, inferior-superior (I-S), inferotemporal-superonasal (IT-SN), and the vertical location of the thinnest cornea. The 1-percentile value of the normal group was used to define the diagnostic cutoff. Placido-ring-based corneal topography was obtained for comparison. MAIN OUTCOME MEASURES The OCT pachymetric parameters and a quantitative topographic keratoconus index (keratometry, I-S, astigmatism, and skew percentage [KISA%]) were used for keratoconus diagnosis. Diagnostic performance was assessed by the area under the receiver operating characteristic (AROC) curve. RESULTS Keratoconic corneas were thinner. The pachymetric minimum averaged 452.6+/-60.9 microm in keratoconic eyes versus 546+/-23.7 microm in normal eyes. The 1-percentile cutoff was 491.6 microm. The thinnest location was inferiorly displaced in keratoconus (-805+/-749 microm vs -118+/-260 microm; cutoff, -716 microm). The thinning was focal (minimum-median: -95.2+/-41.1 microm vs -45+/-7.7 microm; cutoff, -62.6 microm). Keratoconic maps were more asymmetric (I-S, -44.8+/-28.7 microm vs -9.9+/-9.3 microm; cutoff, -31.3 microm; and IT-SN, -63+/-35.7 microm vs -22+/-11.4 microm; cutoff, -48.2 microm). Keratoconic eyes had a higher KISA% index (2641+/-5024 vs 21+/-19). All differences were statistically significant (t test, P<0.0001). Applying the diagnostic criteria of any 1 OCT pachymetric parameter below the keratoconus cutoff yielded an AROC of 0.99, which was marginally better (P = .09) than the KISA% topographic index (AROC, 0.91). CONCLUSIONS Optical coherence tomography pachymetry maps accurately detected the characteristic abnormal corneal thinning in keratoconic eyes. This method was at least as sensitive and specific as the topographic KISA. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Treatment strategies and visual acuity outcomes in chronic postoperative propionibacterium acnes endophthalmitis

PURPOSE To report the treatment strategies and visual acuity outcomes of chronic postoperative endophthalmitis caused by Propionibacterium acnes. DESIGN Retrospective noncomparative case series. PARTICIPANTS All patients presenting 8 or more weeks after cataract surgery with intraocular inflammation caused by culture-proven P. acnes infection and treated at two institutions from 1974 through 1996 were included. METHODS Patients underwent three different initial treatment strategies. The study did not have a defined treatment protocol, but all patients received intraocular antibiotics. Patients were not randomly assigned to the various treatment strategies. MAIN OUTCOME MEASURES Final visual acuity and effectiveness of various treatment procedures either as initial or follow-up therapy were assessed. RESULTS Using the 3 initial strategies, 36 patients were treated: (1) intraocular antibiotic injection alone (IOAB; n = 12); (2) pars plana vitrectomy and IOAB injection (PPV; n = 10); and (3) PPV with subtotal capsulectomy and IOAB injection (PPV-PC; n = 14). The number of patients with recurrent or persistent inflammation after one of the three initial treatment strategies were as follows: (1) IOAB alone, 12 (100%); (2) PPV, 5 (50%); and (3) PPV-PC, 2 (14%). None of the patients that underwent subsequent PPV, total capsular bag removal, IOAB injection, and either intraocular lens (IOL) exchange or removal had persistent or recurrent intraocular inflammation. Overall, final visual acuity was 20/40 or better in 18 patients (50%), and a total of 28 patients (78%) retained 20/400 or better vision. The mean follow-up after the last treatment was 2.9 years. CONCLUSIONS In this series of chronic P. acnes endophthalmitis, initial treatment with IOAB injection alone or vitrectomy without capsulectomy was associated with high rates of recurrent or persistent intraocular inflammation. Pars plana vitrectomy, partial capsulectomy, and IOAB injection without IOL exchange was usually successful on long-term follow-up. In patients with recurrent intraocular inflammation, pars plana vitrectomy, total capsular bag removal, IOAB injection, and IOL exchange or removal was a uniformly successful strategy. In contrast to other types of postoperative endophthalmitis, IOL exchange can be considered in these patients after total capsular bag removal.

Clinical features and associated systemic diseases of HLA-B27 uveitis

PURPOSE To delineate the clinical features, course, complications, and associated systemic diseases in patients with HLA-B27-associated uveitis. METHODS We reviewed the records of 148 patients with HLA-B27-associated uveitis from two large uveitis practices. RESULTS There were 127 (86%) white and 21 (14%) nonwhite patients, and a male-to-female ratio of 1.5:1. The median age at onset of uveitis was 32 years; eight patients (5%) had their first attack after age 55 years. Acute anterior uveitis was noted in 129 patients (87%), and nonacute inflammation was noted in 19 (13%). Ocular involvement was categorized as unilateral or unilateral alternating in 138 patients (93%), but ten patients (7%) had bilateral, concurrent disease. The median duration of an attack was six weeks, and the median number of recurrences for patients with more than 12 months of follow-up was three. Cataracts were associated with posterior synechiae (P = .03), increased intraocular pressure (P = .003), and cystoid macular edema (P = .04). An HLA-B27-associated systemic disorder was present in 83 patients (58%), 30 of whom were women, and it was diagnosed in 43 of the 83 patients as a result of the ophthalmologic consultation. Thirty-four (30%) of 112 patients had a family history of a spondyloarthropathy. CONCLUSIONS Although HLA-B27-associated uveitis is usually described as a disease of young white men, women and nonwhites may also be affected. A subgroup of patients have severe disease and consequently more complications. Most patients have an associated systemic disease, including women, who appear to have more atypical spondyloarthropathies. The systemic diseases were frequently undiagnosed before the onset of the ocular disease and before the uveitis consultation.