Mi Sun Sung

Long-Term Outcome of Treatment with Topical Corticosteroids for Severe Dry Eye Associated with Sjögren's Syndrome

This retrospective study was performed to analyze the long-term outcome of topical corticosteroid treatment for severe dry eye associated with Sjögrens syndrome (SS). Patients who had severe dry eye associated with SS were topically treated with loteprednol etabonate 0.5% (group A, n=66) or fluorometholone 0.1% (group B, n=67) twice daily and were followed up for 2 years. Visual acuity (VA), intraocular pressure (IOP), Schirmer test, tear film breakup time (BUT), keratoepitheliopathy, and symptom scores were measured at baseline and 6, 12, 18, and 24 months after treatment. VA and IOP were not changed significantly during follow-up in either group. Schirmer test results, keratoepitheliopathy, and symptom scores at 6, 12, 18, and 24 months (p<0.05) and tear film BUT at 12, 18, and 24 months (p<0.05) significantly improved after treatment compared with baseline in both groups. No significant differences between the groups were found in any parameter during follow-up. At 24 months, the number of patients with IOP elevation of more than 2 mmHg compared with baseline was 4 in group A (6.1%) and 9 in group B (13.4%). The mean IOP in these patients was lower in group A than in group B (15.00±0.82 mmHg versus 16.50±1.12 mmHg; p=0.04). Long-term application of low-dose topical corticosteroids is effective for controlling signs and symptoms of chronic, severe dry eye associated with SS. Loteprednol etabonate 0.5% may have a lower risk for IOP elevation than fluorometholone 0.1%.

Effect of Topical 5-Aminoimidazole-4-carboxamide-1-β-d-Ribofuranoside in a Mouse Model of Experimental Dry Eye.

PURPOSE To investigate the efficacy of topical 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) in a mouse model of experimental dry eye (EDE). METHODS Eye drops consisting of 0.001% or 0.01% AICAR, 0.05% cyclosporine A (CsA), or balanced salt solution (BSS) were applied for the treatment of EDE. Tear volume, tear film break-up time (BUT), and corneal fluorescein staining scores were measured 10 days after treatment. Levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interferon gamma-induced protein 10 (IP-10), and monokine induced by interferon-γ (MIG) were measured in the conjunctiva. In addition, Western blot, periodic acid-Schiff staining for evaluating goblet cell density, flow cytometry for counting the number of CD4+CXCR3+ T cells, and immunohistochemistry for detection of 4-hydroxy-2-nonenal (4HNE) were performed. RESULTS Mice treated with 0.01% AICAR showed a significant improvement in all clinical parameters compared with the EDE control, vehicle control, and 0.001% AICAR groups (P < 0.001). A significant decrease in the levels of IL-1β, IL-6, TNF-α, IFN-γ, IP-10, and MIG, the number of CD4+CXCR3+ T cells, and the number of 4HNE-positive cells were also observed in the 0.01% AICAR group (P < 0.001). Although 0.05% CsA also led to an improvement in clinical parameters and inflammatory molecule levels, its therapeutic effects were comparable or inferior to those of 0.01% AICAR. CONCLUSIONS Topical application of 0.01% AICAR can markedly improve clinical signs and decrease inflammation in the ocular surface of EDE, suggesting that AICAR eye drops may be used as a therapeutic agent for dry eye disease.

Clinical features of superficial and deep peripapillary microvascular density in healthy myopic eyes

Purpose To evaluate the clinical features of peripapillary microvasculature in myopic eyes and investigate the association between the superficial and deep peripapillary microvascular density and the myopic optic disc characteristics. Materials and methods This cross-sectional study included one hundred and fifty healthy myopic eyes with β-peripapillary atrophy (β-PPA). Ovality index, degree of optic disc rotation, and the area of β-PPA were measured. Superficial and deep peripapillary microvascular density was measured using optical coherence tomography angiography. Logistic regression analysis was performed to look for the factors associated with peripapillary microvascular reduction. Results The mean superficial peripapillary microvascular density was 62.14 ± 5.47%; 33 (22.0%) participants were found to have decreased microvascular density. Increased axial length (p < 0.001) and decreased average peripapillary retinal nerve fiber layer thickness (p = 0.027) were associated with the superficial peripapillary microvascular reduction. The mean deep peripapillary microvascular density was 73.76 ± 4.02%; 26 (17.33%) participants were found to have decreased microvascular density. Larger ovality index (p = 0.028) and more inferiorly rotated optic disc (p = 0.021) were associated with the deep peripapillary microvascular reduction. Conclusions Axial elongation was significantly associated with microvascular reduction in the superficial peripapillary retina, whereas it was not associated with deep peripapillary microvascular reduction. The deep peripapillary microvascular density was independently associated with myopic optic disc characteristics such as ovality index and optic disc rotation.

Factors Affecting Treatment Outcome of Graft Infection Following Penetrating Keratoplasty.

Purpose To evaluate the factors affecting treatment outcome of graft infection following penetrating keratoplasty (PKP). Methods In this retrospective study, 28 patients who underwent PKP between January 2005 and January 2013 and who were diagnosed with graft infection were classified into a treatment success group or a treatment failure group. Demographic and clinical characteristics, as well as the results of the microbiologic investigation, were analyzed and compared. A subsequent binary logistic regression analysis was performed to identify the prognostic factors affecting treatment outcome. Results Graft infection occurred at a mean of 38.29 ± 36.16 months (range, 1 to 96 months) after PKP. Seventeen patients developed bacterial keratitis, and 11 patients developed fungal keratitis. Overall, of the 28 patients, nine (32.1%) were classified in the treatment failure group. Multivariate analysis identified pre-existing graft failure (p = 0.019), interval longer than 72 hours between donor death and PKP (p = 0.010), and fungal infection (p = 0.026) as significant risk factors for treatment failure. Conclusions Pre-existing graft failure, extended interval between donor death and PKP, and fungal infection were important risk factors for treatment failure of graft infection following PKP.

Clinical Features of Ocular Ischemic Syndrome and Risk Factors for Neovascular Glaucoma

Purpose We aimed to examine the clinical features and prognosis of ocular ischemic syndrome and to investigate the risk factors for the development of neovascular glaucoma (NVG). Methods The medical records from 25 patients (25 eyes) who were diagnosed with ocular ischemic syndrome were retrospectively analyzed. We recorded the length of time between symptom onset and diagnosis, visual acuity, intraocular pressure, clinical findings of the anterior and posterior segments of the eye, fluorescein angiography, systemic diseases, smoking history, and the extent of any ipsilateral carotid artery stenosis. The risk factors for NVG in patients with ocular ischemic syndrome were investigated. Results The mean age was 67.9 ± 12.5 years, and 21 men and 4 women were included in this study. At initial examination, the mean logarithm of the minimum angle of resolution (logMAR) was 2.02 ± 1.26, and the mean intraocular pressure was 21.0 ± 10.3 mmHg. Among 25 eyes of the 25 patients, NVG occurred in 17 eyes after a mean period of 12.6 ± 14.0 months. The length of time between symptom onset and diagnosis (p = 0.025) and the extent of ipsilateral carotid artery stenosis (p = 0.032) were identified as significant risk factors for NVG. At the final follow-up, the mean logMAR visual acuity was 3.13 ± 1.24, showing a poor prognosis regardless of whether NVG occurred. Conclusions Overall, the prognosis for ocular ischemic syndrome is very poor. The risk of NVG increases with the length of time between symptom onset and diagnosis, as well as with the severity of ipsilateral carotid artery stenosis.

Association between meibomian gland dysfunction and compliance of topical prostaglandin analogs in patients with normal tension glaucoma

Purpose The aim of this study was to investigate the association between tear film and meibomian gland parameters in patients with normal tension glaucoma (NTG), who underwent topical prostaglandin analog (PGA) monotherapy, and medication compliance. Methods Ocular surface disease index (OSDI), Schirmer’s test, tear film break-up time (TBUT), keratoepitheliopathy (KEP) score with fluorescein, and meibomian gland parameters were assessed in 45 eyes of 45 patients with NTG (NTG group), who received topical PGA monotherapy for more than 1 year. The results were compared to those of 40 eyes of 40 normal subjects (control group). Medication compliance was assessed by an 8-item Morisky Medication Adherence Scale (MMAS-8). Multiple logistic regression analysis was used to identify the factors associated with medication compliance. Results There was a significant difference in OSDI (P = 0.043), Schirmer’s test (P < 0.001), TBUT (P < 0.001), KEP score (P = 0.015) and all meibomian gland parameters (all P < 0.001) between two groups. When the NTG group was divided into compliant and non-compliant groups based on the scores of MMAS-8, 30 (75%) patients were classified into the compliant group. Multiple logistic regression analysis revealed that the lid margin score (OR, 0.256; 95% CI, 0.072–0.908, P = 0.035), meibum score (OR, 0.144; 95% CI, 0.023–0.915, P = 0.04), and meibo score (OR, 0.344; 95% CI, 0.140–0.845, P = 0.02) were significant factors associated with compliance in patients with NTG. The meibomian gland parameters showed a negative correlation with medication compliance (all P < 0.005). Conclusions Malfunction of the meibomian glands can be an important clinical finding associated with compliance of PGA monotherapy in patients with NTG.

Analysis of Clinical Factors Associated with Retinal Morphological Changes in Patients with Primary Sjögren's Syndrome

Purpose To investigate clinical factors associated with abnormal retinal morphologies in patients with primary Sjögrens syndrome (pSS). Methods One-hundred-thirty patients with pSS who underwent immunoserological tests, minor salivary gland biopsies, and optical coherence tomography examinations were retrospectively analyzed. Risk factors for abnormally reduced peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell–inner plexiform layer (mGCIPL) thicknesses were evaluated, as well as the correlation between clinical factors and pRNFL and mGCIPL thicknesses. Results Anti-Sjögrens syndrome type B (SSB) antibody positivity (P = 0.048) was identified as a risk factor associated with abnormally reduced pRNFL thickness, and anti-SSB positivity (P = 0.005) and erythrocyte sedimentation rate (ESR) level (P = 0.031) were identified as risk factors associated with an abnormally reduced mGCIPL thickness as revealed by multivariate logistic regression analysis. There was a significant negative correlation between anti-SSB antibody levels and the thickness of pRNFL and mGCIPL. The thicknesses of pRNFL and mGCIPL were significantly reduced in anti-SSB–positive eyes when compared to anti-SSB–negative eyes (P < 0.05). However, histopathologic grading was not associated with the pRNFL and mGCIPL thicknesses. Conclusion Anti-SSB antibody positivity and ESR levels may be useful for predicting an abnormally reduced pRNFL or mGCIPL thickness in patients with pSS. Our results may provide clinical evidence to substantiate the association between aberrant autoimmunity and inner retinal changes in patients with pSS.

Effect of myopic refractive error on the glaucoma diagnostic ability of cirrus high-definition optical coherence tomography.

tive link between DM and POAG (Gordon et al. 2002). Our study identified a significant CSFP elevation in younger diabetics, a relationship that did not extend beyond the age of 40. Lastly, a link between Alzheimer’s and POAG has been recently examined from the standpoint of retrolaminar CSFP dynamics (Wostyn et al. 2009). Our results identify a significant CSF pressure decrease in middle-age patients with Alzheimer’s disease that abruptly changes to a trend towards increased CSFP (albeit statistically insignificant). Whether this indicates a clinical association or holds significant clinical implications requires additional studies. Future research directed towards understanding CSFP trends in normal and disease populations, and incidence and progression trends in patients with POAG harbouring these respective diseases, may aid in elucidating our current association data.

Factors Influencing Visual Field Recovery after Transsphenoidal Resection of a Pituitary Adenoma

Purpose This study aimed to analyze the factors influencing visual field recovery after transsphenoidal approach-tumor resection (TSA-TR) in pituitary adenoma patients with visual field defects (VFDs). Methods We retrospectively evaluated 102 eyes of 102 patients with VFDs induced by pituitary adenomas who underwent TSA-TR between January 2010 and December 2015. All patients had been observed for more than one year. The severity of the VFD in each patient was evaluated using the mean deviation (MD) and pattern standard deviation in the most-affected eye. Clinical and demographic data such as preoperative visual acuity and visual field, age, sex, tumor volume, neurological symptoms at diagnosis, duration of symptoms, patterns of the preoperative VFD, and preoperative central VFD were investigated and analyzed for association with recovery of the visual field. Results Recovery from VFDs occurred in 71 (69.6%) eyes after a mean period of 18.36 ± 5.21 months. The recovery group was younger (p = 0.003), had higher preoperative MD values (p = 0.016), and had better preoperative visual acuity (p = 0.03), compared with the non-recovery group. Preoperative central VFD (p = 0.006) and preoperative bilateral VFD (p = 0.016) were significantly less frequent in the recovery group. Multivariate logistic regression revealed that age at diagnosis (odds ratio [OR], 0.962; p = 0.022), preoperative MD (OR, 1.069; p = 0.046), preoperative central VFD (OR, 0.212; p = 0.039), and preoperative bilateral VFD (OR, 0.212; p = 0.035) were associated with visual field recovery after TSA-TR. Conclusions Younger age, higher preoperative MD, and the preoperative abscence of central VFD or bilateral VFD were favorable factors influencing visual field recovery after TSA-TR in patients with pituitary adenomas. An understanding of the associated clinical factors may help predict visual outcomes after TSA-TR in pituitary adenoma patients with VFDs.

Trichostatin A Ameliorates Conjunctival Fibrosis in a Rat Trabeculectomy Model

Purpose To investigate whether histone deacetylase (HDAC) activity is associated with postoperative scarring and to evaluate the effect of HDAC inhibition by topical trichostatin A (TSA) on conjunctival fibrosis after trabeculectomy in a rat model. Methods Trabeculectomy was performed on the left eye of Sprague-Dawley rats. In the first experiment, adenoviruses HDAC 1, HDAC 2, and green fluorescent protein were added to the subconjunctival space during trabeculectomy. Expression of α-smooth muscle actin (α-SMA) was evaluated. In the second experiment, rats undergoing trabeculectomy were randomized into control, vehicle control, steroid, 500 nmol/L TSA, and 1 μmol/L TSA groups. On postoperative day 14, bleb vascularity, toxic effect of topical TSA on corneal epithelium, expression of α-SMA, transforming growth factor (TGF)-β1, and phosphorylated-Smad2/3 and the infiltration of CD45+ cells were determined. Massons trichrome staining and immunofluorescence staining for α-SMA and CD45 were also performed. Results Overexpression of HDAC1 contributed to accelerated conjunctival fibrosis after trabeculectomy. HDAC inhibition by topical administration of 1 μmol/L TSA significantly decreased bleb vascularity, leukocyte infiltration, and expression of α-SMA and TGF-β1 in the conjunctiva. Its effectiveness on conjunctival fibrosis was comparable to that of topical steroid. Massons trichrome staining showed decreased collagen deposition in the bleb tissues of steroid and 1 μmol/L TSA treatment groups. Topical TSA did not have any toxic effect on the corneal epithelium. Conclusions HDAC activity is involved in postoperative conjunctival fibrosis. HDAC inhibition by topical administration of TSA eye drops is a safe and effective therapeutic modality to modulate wound healing after trabeculectomy.