Andrew J.W. Huang

Evaluation of corneal thickness and topography in normal eyes using the Orbscan corneal topography system

AIMS To map the thickness, elevation (anterior and posterior corneal surface), and axial curvature of the cornea in normal eyes with the Orbscan corneal topography system. METHODS 94 eyes of 51 normal subjects were investigated using the Orbscan corneal topography system. The anterior and posterior corneal elevation maps were classified into regular ridge, irregular ridge, incomplete ridge, island, and unclassified patterns, and the axial power maps were grouped into round, oval, symmetric bow tie, asymmetric bow tie, and irregular patterns. The pachymetry patterns were designated as round, oval, decentred round, and decentred oval. RESULTS The thinnest point on the cornea was located at an average of 0.90 (SD 0.51) mm from visual axis and had an average thickness of 0.55 (0.03) mm. In 69.57% of eyes, this point was located in the inferotemporal quadrant, followed by the superotemporal quadrant in 23.91%, the inferonasal quadrant in 4.35%, and the superonasal quadrant in 2.17%. Among the nine regions of the cornea evaluated (central, superotemporal, temporal, inferotemporal, inferior, inferonasal, nasal, superonasal, and superior) the central cornea had the lowest average thickness (0.56 (0.03) mm) and the superior cornea had the greatest average thickness (0.64 (0.03) mm). The mean simulated keratometry (SimK) was 44.24 (1.61)/43.31 (1.66) dioptres (D) and the mean astigmatism was 0.90 (0.41) D. Island (71.74%) was the most common elevation pattern observed in the anterior corneal surface, followed by incomplete ridge (19.57%), regular ridge (4.34%), irregular ridge (2.17%), and unclassified (2.17%). Island (32.61%) was the most common topographic pattern in the posterior corneal surface, following by regular ridge (30.43%), incomplete ridge (23.91%), and irregular ridge (13.04%) patterns. Symmetric bow tie was the most common axial power pattern in the anterior cornea (39.13%), followed by oval (26.07%), asymmetric bow tie (23.91%), round (6.52%), and irregular (4.53%) patterns. In the pachymetry maps, 47.83% of eyes had an oval pattern, and round, decentred oval, and decentred round were observed in 41.30%, 8.70%, and 2.18% of eyes, respectively. CONCLUSION The information on regional corneal thickness, corneal elevation and axial corneal curvature obtained with the Orbscan corneal topography system from normal eyes provides a reference for comparison with diseased corneas. The Orbscan corneal topography system is a useful tool to evaluate both corneal topography and corneal thickness.

Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjögren’s syndrome

Sjögrens syndrome is a common autoimmune disease (affecting ∼0.7% of European Americans) that typically presents as keratoconjunctivitis sicca and xerostomia. Here we report results of a large-scale association study of Sjögrens syndrome. In addition to strong association within the human leukocyte antigen (HLA) region at 6p21 (Pmeta = 7.65 × 10−114), we establish associations with IRF5-TNPO3 (Pmeta = 2.73 × 10−19), STAT4 (Pmeta = 6.80 × 10−15), IL12A (Pmeta = 1.17 × 10−10), FAM167A-BLK (Pmeta = 4.97 × 10−10), DDX6-CXCR5 (Pmeta = 1.10 × 10−8) and TNIP1 (Pmeta = 3.30 × 10−8). We also observed suggestive associations (Pmeta < 5 × 10−5) with variants in 29 other regions, including TNFAIP3, PTTG1, PRDM1, DGKQ, FCGR2A, IRAK1BP1, ITSN2 and PHIP, among others. These results highlight the importance of genes that are involved in both innate and adaptive immunity in Sjögrens syndrome.

Conjunctival Cytologiec Features of Primary Sjögren's Syndrome

Abstract To determine whether there are specific cytologic features associated with primary Sjogrens syndrome (SS), the authors evaluated impression cytology specimens from three conjunctival sites (temporal bulbar [TB], inferior bulbar [IB], and inferior tarsal [IT]) from 38 SS eyes, 34 eyes of aqueous tear-deficient patients without SS, 35 eyes of seborrheic blepharitis patients, and 17 eyes of normal controls in a masked fashion. The following features were observed more frequently in SS eyes than in the eyes of the other groups: squamous metaplasia of the TB and IB ( P 75%) goblet cell loss of the TB ( P P P P

TRANSFORMING GROWTH FACTOR BETA-1 AND BETA-2 IN HUMAN TEAR FLUID

PURPOSE To evaluate human tear fluid for transforming growth factor beta isoforms 1 and 2 (TGF-beta1 and TGF-beta2). METHODS To accomplish this, human tears were evaluated for TGF-betas by quantitative antibody sandwich ELISA (sELISA), mink lung epithelial cell (MLEC) growth inhibition bioassay and western blotting. Various physical and chemical treatments were used to activate TGF-beta in these assays. RESULTS TGF-betas could not be detected in untreated or heated tears by sELISA; however, mean TGF-beta1 concentrations of 2.32 ng/ml were detected in acid-activated tears by sELISA. Furthermore, 10.54 ng/ml of TGF-beta1 and 2.98 ng/ml of TGF-beta2 were detected in tears treated with the mucolytic agent, acetylcysteine. Total TGF-beta bioactivity in human tears measured by the MLEC assay was found to be 13.04 ng/ml in untreated tears and 24.85 ng/ml in acid-activated tears. Approximately one-half TGF-beta in tear specimens was biologically active (mean = 52%, range 39-71%). Total tear TGF-beta bioactivity could be completely neutralized by recombinant human TGF-beta1 latency associated peptide (rh TGF-beta1 LAP). Mean neutralization of tear TF-beta bioactivity was 83% by TGF-beta1-specific antisera, and was 13% by TBF-beta2-specific antisera. Immunoreactive TBF-beta bands at approximately 12.5 and 95 kD were observed in immunoblots of reduced acidified tears. A high molecular weight (MW) TGF-beta band (>203 dD) was noted in untreated tears; however, this band disappeared following treatment with acetylcysteine. CONCLUSIONS The results of these studies indicate that TGF-beta1 and TGF-beta2 are present in human tear fluid, and TGF-beta1 is the predominant isoform. There appear to be factors in human tears capable of binding TGF-beta.

Prevalence, severity, and predictors of fatigue in subjects with primary Sjögren's syndrome

OBJECTIVE To investigate the relationship of fatigue severity to other clinical features in primary Sjögrens syndrome (SS) and to identify factors contributing to the physical and mental aspects of fatigue. METHODS We identified 94 subjects who met the American-European Consensus Group criteria for the classification of primary SS. Fatigue was assessed with a visual analog scale, the Fatigue Severity Scale (FSS), and the Profile of Fatigue (ProF). Associations with fatigue were compared using multivariate regression. RESULTS Abnormal fatigue, defined as an FSS score >or=4, was present in 67% of the subjects. Pain, helplessness, and depression were the strongest predictors of fatigue according to the FSS and the somatic fatigue domain of the ProF (ProF-S), both with and without adjustment for physiologic and serologic characteristics. Depression was associated with higher levels of fatigue; however, the majority of subjects with abnormal fatigue were not depressed. Anti-Ro/SSA-positive subjects were no more likely to report fatigue than seronegative subjects. The regression models explained 62% of the variance in FSS and 78% of the variance in ProF-S scores. Mental fatigue was correlated with depression and helplessness, but the model predicted only 54% of the variance in mental fatigue scores. CONCLUSION Psychosocial variables are determinants of fatigue, but only partially account for it. Although fatigue is associated with depression, depression is not the primary cause of fatigue in primary SS. Investigation of the pathophysiologic correlates of physical and mental aspects of fatigue is needed to guide the development of more effective interventions.

Mycobacterium interface keratitis after laser in situ keratomileusis

PURPOSE To report the clinical course, management, and outcome of infectious interface keratitis caused by mycobacterium species after laser in situ keratomileusis (LASIK). DESIGN A small noncomparative interventional case series. PARTICIPANTS Five eyes in four patients who underwent LASIK in different locations around the world and had culture-positive mycobacterium keratitis develop. INTERVENTION The LASIK flap was lifted or amputated, samples were submitted for Ziehl-Neelsen acid-fast stain and Lowenstein-Jensens agar cultures for diagnosis; topical treatment with fortified clarithromycin and amikacin was administered until clinical resolution. MAIN OUTCOME MEASURES Time periods from onset to diagnosis and from diagnosis to clinical resolution, and the final visual acuity. RESULTS Onset of symptoms of infection occurred after a mean of 20 days (range, 11 days-6 weeks) after LASIK or an enhancement procedure. Definitive diagnosis was obtained after a mean period of 4.5 weeks (range, 12 days-8 weeks) from onset. Keratitis resolved within 8.4 weeks (range, 1-18 weeks) of treatment with fortified clarithromycin and amikacin. Corticosteroids were found to worsen and prolong the course of disease. In four of five eyes the LASIK flap was amputated. CONCLUSIONS Mycobacterial keratitis is a potentially vision-threatening complication after LASIK, characterized by a long latent period, delayed diagnosis, and a protracted course even under intensive specific antibiotic therapy. Inclusion of specific culture media and staining protocols for mycobacteria, along with aggressive treatment on diagnosis, including lifting or amputating the LASIK flap, culturing, topical fortified clarithromycin and amikacin, while avoiding corticosteroids, may significantly improve resolution of the infection and potentially improve the visual outcome.

Induction of Conjunctival Transdifferentiation on Vascularized Corneas by Photothrombotic Occlusion of Corneal Neovascularization

Previous studies have established that conjunctival transdifferentiation (transformation into cornea-like morphology) is inhibited by corneal vascularization. Conversely, occlusion of corneal vessels may induce conjunctival transdifferentiation on vascularized corneas. To test this hypothesis, the corneal epithelia of New Zealand albino rabbits were debrided 3 mm beyond the limbus with n-heptanol. Sixteen corneas healed by conjunctival epithelium, with vascularization persisting for 20 months, were used in this study. Photochemically induced occlusion of the corneal vessels was achieved by intravenous administration of rose bengal-saline solution (40 mg/kg body weight) with subsequent argon laser irradiation of the vessels (514.5 nm, 130 mW, 63 micron and 0.2 sec). The treated vessels remained occluded in an 18-week study, as confirmed by corneal fluorescein angiography. Corneal clarity and epithelial integrity were improved after treatment. Goblet cell loss and morphologic transformation into a cornea-like epithelium were verified by flat-mount preparations, histology, impression cytology, and immunofluorescence studies using a mucin-specific monoclonal antibody. These results indicate that conjunctival transdifferentiation can be induced on vascularized corneas after occlusion of corneal vessels by photothrombosis.

Association of Herpes Zoster Ophthalmicus With Acquired Immunodeficiency Syndrome and Acute Retinal Necrosis

We conducted a review to investigate the prevalence of human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS), in patients with herpes zoster ophthalmicus, as well as the incidence of acute retinal necrosis after herpes zoster ophthalmicus. All charts of patients seen at our institution between 1987 and 1992 with a primary diagnosis of herpes zoster ophthalmicus were reviewed. Of 112 patients with herpes zoster ophthalmicus, 29 (26%) had HIV or AIDS. All these patients were younger than 50 years at the time of diagnosis. Five of 29 (17%) immunocompromised patients had acute retinal necrosis after herpes zoster ophthalmicus. No acute retinal necrosis was identified in the nonimmunocompromised patients after herpes zoster ophthalmicus. We recommend that all patients younger than 50 years who have herpes zoster ophthalmicus at initial examination be tested for HIV. Additionally, HIV-infected patients should be monitored closely after herpes zoster ophthalmicus for development of acute retinal necrosis. Long-term oral prophylactic as well as initial high-dose intravenous acyclovir may be appropriate in HIV-infected individuals with herpes zoster.

Bilateral herpetic keratoconjunctivitis

PURPOSE To review the clinical characteristics and visual outcomes of patients with bilateral herpetic keratitis. DESIGN Retrospective, noncomparative, observational case series. PATIENTS AND METHODS A retrospective review of medical records of 544 patients with herpes simplex virus (HSV) eye disease treated between January 1996 and September 2001 was performed at the Department of Ophthalmology, University of Minnesota. Seven patients (1.3%) with bilateral herpetic keratoconjunctivitis were identified. RESULTS In these seven patients, the age at the initial onset of corneal disease ranged from 7 weeks to 46 years, with a median of 18 years and a mean of 19.3 years. Five patients had systemic atopy, and two patients had severe ocular rosacea. Systemic immune disorders were noted in two patients. Recurrent blepharoconjunctivitis was noted in 8 eyes (57%), epithelial keratitis in 12 eyes (85.7%), stromal keratitis in 9 eyes (64.3%), necrotizing stromal keratitis in 5 eyes (35.7%), and progressive endotheliitis in 2 eyes (14.2%). Corneal complications included opacification, neovascularization, and corneal thinning or perforation. Penetrating keratoplasty was performed in 1 eye, in which endophthalmitis subsequently developed and which required enucleation. Four patients with continued use of oral antiviral prophylaxis (acyclovir 400 mg twice daily) since September 1999 showed significant decreases in recurrence. The average remission in these four patients was 1.7 years. The visual acuity at the last follow-up was 20/40 or worse in 6 eyes (42.8%). CONCLUSIONS In contrast to unilateral HSV keratitis, our patients with bilateral herpetic corneal infections had underlying atopy or immune deviations and evinced more protracted clinical courses. Long-term prophylactic antiviral treatment has reduced the incidence of recurrence in this group of patients.

Effective Treatment of Phlyctenular Keratoconjunctivitis with Oral Tetracycline

PURPOSE To determine the clinical characteristics, possible etiologic agents, and response to oral antibiotic therapy in patients with phlyctenular keratoconjunctivitis. METHODS The authors reviewed the medical records of the 17 patients with phlyctenular keratoconjunctivitis who were seen and treated at the Bascom Palmer Eye Institute between 1981 and 1991. RESULTS All 17 patients were younger than 18 years of age at the onset of their disease. Girls (n = 14) outnumbered boys (n = 3) 4:1. Significant incapacitating symptoms and ocular morbidity occurred frequently, including three perforated corneas. Five of ten patients who were tested for Chlamydia infection had positive test results and five patients possibly had early rosacea dermatitis. All patients experienced long-term remission of their ocular disease after a course of oral tetracycline or erythromycin. Two patients demonstrated unique linear (fascicular) corneal phlyctenules. CONCLUSION Oral tetracycline or erythromycin treatment produces long-lasting remission of phlyctenular keratoconjunctivitis in affected children.