Sung Huei Tseng

Erythema multiforme, Stevens-Johnson Syndrome, and toxic epidermal necrolysis: Acute ocular manifestations, causes, and management

Purpose: To study the acute ocular/cutaneous manifestations, causes, and management of the erythema multiforme (EM)/Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) disease spectrum. Methods: We retrospectively reviewed the medical records of all EM/SJS/TEN patients hospitalized at National Cheng Kung University Hospital in Taiwan between 1988 and 2004. Demographic data, medical/medication histories, ocular/mucocutaneous manifestations, management, sequelae, and recurrence were analyzed. Results: A total of 207 patients 2 months to 95 years of age were hospitalized with 213 episodes/attacks of EM/SJS/TEN. Medications were the most common cause of any condition: for SJS, carbamazepine was most common; for EM or TEN, allopurinol was most common. In 128 of the 213 attacks (60.1%; 126 patients), ocular manifestations were documented during hospitalization, occurring more often in those with SJS (81.3%) or TEN (66.7%) compared with those with EM (22.7%; P < 0.01). The most frequent ocular treatments were topical steroids, topical antibiotics, and lubricants. Overall, 24 (18.8%) of 128 acute attacks in 126 patients were followed by ocular sequelae, mostly dry eye. Five (2.4%) of the 207 patients sustained a total of 6 recurrent attacks, in 3 cases because of the same medication. Conclusions: Ocular manifestations occur in a high proportion of patients with EM/SJS/TEN. The most frequent causes were carbamazepine and allopurinol. A careful medication history should be obtained from these patients. Ophthalmic consultation, evaluation, and management are mandatory.

Effect of artificial tears on corneal surface regularity, contrast sensitivity, and glare disability in dry eyes

OBJECTIVE To investigate the effects of artificial tears on corneal surface regularity and visual function in dry eyes. DESIGN Nonrandomized, comparative trial. PARTICIPANTS Forty patients (40 eyes) with dry eyes with (group 1, n = 15 eyes) or without (group 2, n = 25 eyes) punctate epithelial keratopathy and a normal control group of 20 individuals (20 eyes) with no ocular abnormalities (group 3). METHODS In both dry and normal eyes, the surface regularity index (SRI), surface asymmetry index (SAI), and potential visual acuity (PVA) were measured by computer-assisted videokeratography (TMS-1; Computed Anatomy, New York, NY). Spatial-contrast sensitivity and glare disability were also measured before and 1 minute after instillation of artificial tears. MAIN OUTCOME MEASURES Differences in SRI, SAI, PVA, spatial-contrast sensitivity, and glare disability between groups, before instillation of tears, and within groups, after instillation of tears. RESULTS Compared with group 3, eyes in group 1 had significantly worse SRI, SAI, PVA, and contrast sensitivity (incomplete glare disability data precluded analysis) before instillation of artificial tears. Differences in corneal surface regularity and visual function between groups 2 and 3 were not significant except for a significantly increased glare disability at low spatial frequency (1.5 cycles per degree [cpd]) in group 2. Significant improvement in SRI, SAI, PVA, and contrast sensitivity were observed after instillation of artificial tears in group 1. In groups 2 and 3, the only significant changes were improvement in glare disability at 1.5 cpd and worsening of the SRI, respectively. CONCLUSIONS Tear film changes in dry eye patients may lead to irregularities on the corneal surfaces, causing glare disability. However, these changes may be too subtle in the early stages of dry eyes to be detected by corneal topography or contrast sensitivity measurements. Significant improvement in SRI, SAI, PVA, and contrast sensitivity were found after instillation of artificial tears in dry eyes with punctate epithelial keratopathy.

Comparison of dyes for cataract surgery. Part 1 Cytotoxicity to corneal endothelial cells in a rabbit model

Purpose: To investigate the corneal endothelial cytotoxicity of dyes for capsule staining in cataract surgery. Setting: Department of Ophthalmology and Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan. Methods: Cultured corneal endothelial cells of New Zealand white rabbits were exposed for 1 minute to 1 of the following dyes (various concentrations): indocyanine green (ICG), methylene blue (MB), gentian violet (GV), trypan blue (TB), and fluorescein sodium (FS). The degree of cell damage was determined by in vitro staining with TB and comparison with results in a control group. The effect of longer exposure (up to 10 minutes) to ICG 0.25% was also investigated. Structural changes in corneal endothelial cells after dye exposure were evaluated by light microscopy and transmission electron microscopy (TEM). Results: Indocyanine green 0.25%, MB 0.20%, GV 0.01%, TB 0.40%, and FS 10% did not induce significant damage to corneal endothelial cells. Significant cytotoxicity was observed with the following or higher dye concentrations: ICG 0.50%, MB 0.50%, and GV 0.10%. Exposure to ICG 0.25% for 1 to 10 minutes showed a trend toward cytotoxicity after 10 minutes. On TEM, corneal endothelial cells that had been exposed to ICG 0.50% showed remarkable organelle swelling and disruption, electron‐dense granules, and cell lysis. Conclusion: One minute of exposure to ICG 0.25%, MB 0.20%, GV 0.01%, TB 0.40%, and FS 10% appeared to be safe as determined by no cytotoxic effects on rabbit corneal endothelial cells in culture.

Management of infectious scleritis after pterygium excision

PURPOSE We sought to describe the clinical features, responsible pathogens, management, and prognosis of infectious scleritis after pterygium excision. METHODS A retrospective study through review of medical records of patients diagnosed with infectious scleritis after pterygium excision over a 10-year period at our institution. RESULTS A total of 16 cases of infectious scleritis after pterygium excision was identified. Among them, eight were associated with sclerokeratitis, and six had multifocal scleral nodules with subconjunctival abscesses. Culture results were positive in 15 (93.8%) cases. Pseudomonas was isolated in 13 (81.3%) patients, fungus in three (18.8%), and two had a mixed growth (12.5%). Based on the in vitro susceptibility test, four (31%) Pseudomonas isolates were resistant to gentamicin, whereas all isolates were sensitive to amikacin. During the course of treatment, eight cases were complicated by vitreous opacity, four developed glaucoma, four had serous retinal or choroidal detachment, and two had secondary cataract. Scleral infection recurred in two patients after cessation of therapy. Among the nine patients treated with medical therapy, two eyes were enucleated, whereas only two attained a visual acuity of > or =2/200 at the end of the follow-up period. On the other hand, seven patients had combined antibiotic therapy and surgical debridement. The number of surgical debridement ranged from one to three, with an average of 1.4. In this combined-treatment group, only one patient required enucleation, and five cases attained a visual acuity of > or =2/200. The duration of hospitalization for patients with combined treatment was 21.2+/-4.8 days compared with the 28.4+/-5.0 days for those with medical treatment alone (p = 0.035). CONCLUSION Surgical debridement in combination with appropriate antimicrobial therapy shortens the course of treatment and improves the visual outcome of severe infectious scleritis after pterygium excision.

Cytotoxicity of lidocaine or bupivacaine on corneal endothelial cells in a rabbit model

Purpose: To investigate the corneal endothelial cytotoxicity of commercial formulations of agents used for intracameral anesthesia in cataract and other ocular surgery. Methods: Cultured corneal endothelial cells (CECs) of New Zealand White rabbits were exposed for 1 minute to balanced salt solution (control); Xylocaine (lidocaine) 1% E (with epinephrine), 2% E, 2%, or 4%; or Marcaine (bupivacaine) 0.5% or 0.5% spinal heavy. The degree of cytotoxicity was determined by in vitro staining with trypan blue and light microscopic evaluation of cell morphology. The effect of longer exposure (up to 16 minutes) to lidocaine 1% E was also investigated. Results: CECs were not significantly damaged by 1-minute exposure to lidocaine 1% E or 2% E; however, significant cytotoxicity was seen after 1-minute exposure to lidocaine 2% or 4% or bupivacaine 0.5% or 0.5% spinal heavy. Exposure to lidocaine 1% E showed a trend toward time-dependent cytotoxicity that reached significance at 16 minutes. Conclusions: One-minute exposure to lidocaine 1% E or 2% E appears to be safe for cultured rabbit CECs, although longer exposures could cause time-dependent cytotoxicity, which should be considered in planning cataract or other ocular surgery. Because bupivacaine 0.5% and 0.5% spinal heavy cause cytotoxic effects within the first minute of contact with CECs, they should be used with great caution, if at all, in the anterior chamber of human eyes.

Major Pediatric Ocular Trauma in Taiwan

PURPOSE To investigate major pediatric ocular trauma in Taiwan. METHODS Retrospective review of medical records of all patients 15 years and younger who were hospitalized with a primary diagnosis of eye injury at National Cheng Kung University Hospital, Taiwan, between June 1988 and May 2006. RESULTS There were 156 children (156 eyes) 1.1 to 15.0 years (mean+/-standard deviation, 7.1+/-0.3 years; boy: girl ratio: 2.1:1). Objects most often causing penetrating injury were scissors (13.5%), pencils/pens (12.2%), broken eyeglasses/spectacles (7.7%), and knives (6.4%). Most blunt trauma occurred in traffic accidents (5.8%). Most injuries occurred at home, followed by on the street, at school, and at sports venues. Injuries were classified as open globe (71.2%), adnexal only (18.6%), or closed globe (10.3%), and included corneal laceration (40.4%), lens damage (27.6%), hyphema (25.6%), and eyelid laceration (23.7%). Most surgical procedures were primary repair (88.5%) or removal of a damaged lens (22.4%). Additional surgery was performed in 19.9% of cases. After treatment, 56.4% of eyes had corneal opacity/scar and 7.1% became phthitic; 52.6% had good visual outcome, whereas 23.1% had poor final vision. Compared with visual acuity measured on admission, final visual acuity was improved in 76.1%, unchanged in 19.7%, and worse in 4.3%. Predictors of worse outcome were open-globe injury and larger wound size, posterior segment involvement, and presence of an intraocular foreign body. CONCLUSIONS Most of the children hospitalized for major ocular trauma are younger boys with penetrating injuries suffered at home. Most injuries could have been prevented by increased awareness and reduction of risk factors, and the authors urge better public education for improved safety.

Pigment Epithelium-Derived Factor Gene Met72Thr Polymorphism Is Associated With Increased Risk of Wet Age-related Macular Degeneration

PURPOSE To investigate the Met72Thr (T/C) polymorphism (rs1136287) of pigment epithelium-derived factor (PEDF) gene exon 3 in unrelated Taiwan Chinese patients with late age-related macular degeneration (AMD) and control subjects without AMD. DESIGN Retrospective case-control study. METHODS We enrolled 190 unrelated Taiwan Chinese patients with late AMD and 90 age- and gender-matched control subjects. Grading of late AMD was classified based on a standardized set of diagnostic criteria established by the International Age-Related Maculopathy Epidemiologic Study. Late AMD was classified as either atrophic (dry, grade 4) or neovascular (wet, grade 5). Atrophic AMD refers to dry late-stage AMD without neovascularization, and wet AMD refers to neovascular AMD. Genomic deoxyribonucleic acid was prepared from peripheral blood obtained from all AMD patients and control subjects. Polymerase chain reaction analysis was used to analyze this polymorphism. RESULTS Of the 190 participants with late AMD, atrophic AMD was diagnosed in 104 patients and wet AMD was diagnosed in 86 patients. The genotype distribution of the Met72Thr (T/C) variant of PEDF was TT (homozygous T), TC (heterozygous), and CC (homozygous C). The T allele was found significantly more frequently in wet AMD patients than in controls (50% vs 31%; P =.0005). The allele frequencies in atrophic AMD (30%) and controls (31%) did not differ significantly (all P = .87). The homozygous T genotype was more prevalent in wet AMD than in controls (26/86 [30%] vs nine/90 [10%]; odds ratio, 3.9; all P = .0015). The homozygous T genotype in atrophic AMD patients (8%) and controls (10%) did not differ significantly (all P = .75). CONCLUSIONS Our data suggest that the PEDF Met72Thr T allele may be a risk factor for wet AMD in the Taiwan Chinese population. PEDF may play a role in the pathogenesis of wet AMD.

In vitro benzyl alcohol cytotoxicity: Implications for intravitreal use of triamcinolone acetonide

The aim of the study was to investigate the toxicity of benzyl alcohol (BA), the preservative in commercial triamcinolone acetonide (TA) suspensions, on retinal pigment epithelial (RPE) cells. Cultured RPE cells from a human cell line (ARPE-19) and from rabbits were exposed to the balanced salt solution (control) or BA (0.0225, 0.225, 0.9, 3 or 9mg/mL) for 5, 30, 60, or 120min. Morphological changes of RPE cells were evaluated by the trypan blue in situ staining. The proportions of dead cells were quantitatively measured by the trypan blue exclusion assay, and those of functional cells were assessed by a mitochondrial dehydrogenase assay. The mechanism of cytotoxicity was determined by the acridine orange/ethidium bromide staining and DNA laddering technique. Furthermore, ultrastructural changes were observed by transmission electron microscopy. The results showed that RPE cell damage was dose- and time-dependent. BA 0.225mg/mL, the clinically relevant concentration in TA following intravitreal injection, caused ultrastructural damage and impaired human RPE cell function at 2h; but BA 0.0225mg/mL did not. BA 9.0mg/mL, the concentration in commercial TA suspensions, was toxic within 5min on each assay for both human and rabbit RPE cells. The major mechanism of cell death was necrosis. In conclusion, BA in commercial TA suspensions injected intravitreally (0.225-9mg/mL) can damage RPE cells. Our in vitro study on benzyl alcohol cytotoxicity has significant clinical implications for intravitreal use of TA. We suggest that, before a commercial TA solution is used intravitreally, the vehicle should be removed to prevent damaging the RPE layer, particularly during macular hole surgery. Commercial development of a preservative-free TA suspension for intraocular use is urged.

Impression cytology study of conjunctival epithelial phenotypes on the healing ocular surface after pterygium excision

Purpose. To compare the process of conjunctival epithelial regeneration after three types of pterygium excision procedures. Methods. Thirty-eight patients (45 eyes) with primary pterygium were randomly assigned to a bare-sclera procedure (group 1, 15 eyes of 12 patients), bare-sclera with intraoperative mitomycin C (MMC 0.02% for 30 seconds; group 2, 15 eyes of 14 patients), or pterygium excision with conjunctival autografting (group 3, 15 eyes of 12 patients). Controls were healthy fellow eyes and seven eyes of age-and sex-matched subjects. Impression cytology was performed preoperatively, at 1 and 2 weeks, and at 1, 3, 6, and 12 months after surgery. The nucleus-to-cytoplasm (N/C) ratio of nongoblet epithelial cells and goblet cell density (GCD) in the pterygial area were calculated and compared over time across treatment groups. Results. Pterygium excision wounds healed in a similar four-stage process in all groups, but at different rates and with different final results. The N/C ratio was highest at about 1 month postoperatively in groups 1 and 2 and at 2 weeks in group 3, before gradually returning to control levels. Preoperatively, the GCD in treated eyes was almost twice that in control eyes (p = 0.001) but fell to zero immediately postoperatively. Goblet cells first appeared (with the most rapidly increased density) in group 3, followed by group 1. At 12 months, the mean GCD in groups 1 and 3 were not significantly different from those in controls, whereas the mean GCD in group 2 was still less than that of control (p = 0.02). Conclusions. Healing of conjunctiva is delayed by MMC and is promoted by autografting. Even 1 year after surgery, the ocular surface remains abnormal with respect to epithelial phenotypes in eyes treated by any of the three techniques.

Triamcinolone acetonide suspension toxicity to corneal endothelial cells.

PURPOSE: To investigate the cytotoxicity of triamcinolone acetonide (TA) suspensions to corneal endothelial cells (CECs). SETTING: Department of Ophthalmology, Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan. METHODS: New Zealand white rabbit CECs were exposed for 1 minute to balanced salt solution (BSS); commercial TA suspension (cTA); vehicle‐removed TA (–vTA); pure vehicle (V); 1/10 dilutions of cTA, –vTA, or V in BSS; or benzyl alcohol (BA) (cTA preservative) 9 mg/mL. Corneal endothelial cell toxicity was assessed by light microscopy (trypan blue staining) and transmission electron microscopy. The effects of 3‐, 10‐, or 30‐minute exposures to 1/10 cTA, 1/10 –vTA, or V were also investigated. RESULTS: One‐minute exposures to –vTA or 1/10 –vTA did not damage CECs; however, cTA, V, or 1/10 dilutions of cTA or V caused damage and cells exposed to BA showed severe ultrastructural damage/lysis. A 30‐minute exposure to 1/10 –vTA did not cause significant cell damage, whereas 3‐ to 30‐minute exposures to 1/10 cTA or V showed significant time‐dependent cytotoxicity. CONCLUSIONS: Commercial TA suspension was cytotoxic to cultured rabbit CECs because of the preservative, BA, in the vehicle. Because 1/10 –vTA appeared to be safe for up to 30 minutes of exposure, use of 1/10 dilutions of vehicle‐removed TA is suggested to help surgeons visualize prolapsed vitreous during anterior vitrectomy in complicated cataract surgeries.