A Comprehensive Assessment of Tear-Film-Oriented Diagnosis (TFOD) in a Dacryoadenectomy Dry Eye Model.

Tear film instability is a major cause of dry eye disease. In order to treat patients with short tear film breakup time (TBUT)-type dry eye, the development of tear film stabilizing agents is essential. However, the lack of an appropriate animal model of tear film instability has made drug development difficult. Although rabbit dry eye models have been reported in the past, there are only a few reports that focus on tear film instability. Herein, we assessed the tear film stability of a rabbit dry eye model induced by dacryoadenectomy. A clinical evaluation of the ocular surface, interferometry, and histological assessments of the cornea and conjunctiva were performed. Following the removal of the lacrimal glands, TBUT was shortened significantly, with dimple and random breakup patterns prominently observed. Furthermore, the blink rate in this model increased after dacryoadenectomy, suggesting that this model partially captured the phenotypes of human short TBUT-type dry eye and may be useful as an animal model for investigating potential drug candidates.

Aberrant Corneal Homeostasis in Neurosurgery-Induced Neurotrophic Keratopathy.

The characteristic features of neurotrophic keratopathy have been well documented by in vivo and in vitro studies using animal models. However, case reports of neurotrophic keratopathy induced by neurosurgery are limited. We describe the clinical characteristics, anterior segment optical coherence tomography (AS-OCT) and in vivo confocal microscopy (IVCM) findings of neurotrophic keratopathy induced by surgery for intracranial lesions. This is a case series including 6 eyes of 3 patients (mean age, 69.67 ± 12.50 years) with unilateral neurotrophic keratopathy. The clinical findings of three patients were described and IVCM findings of three patients were analyzed. The duration of neuropathy ranged from 2 to 30 years (median, 22 years). Thickening of the epithelial layer and higher reflection density of the anterior stroma were observed during the healing process using AS-OCT. The mean nerve fiber density of the subepithelial plexus, as determined by IVCM, was 1943 ± 1000 µm/mm2 for neurotrophic eyes and 2242 ± 600.3 µm/mm2 for contralateral eyes (p = 0.0347). The mean respective dendritic cell densities were 30.8 ± 21.8 and 6.25 ± 5.59 cells/mm2 (p < 0.0001), while the mean basal cell sizes were 259 ± 86.5 and 185 ± 45.9 µm2 (p < 0.0001), respectively. These findings suggest that neurosurgery-induced neurotrophic keratopathy may be associated with alterations in the healing process and immune cell distribution in the cornea.

The Effect of Cytokine-Stimulation and Pharmacologic Intervention on PGE2 Production in Primary Human Conjunctival and Corneal Cells.

We studied the production of PGE2 by human conjunctival and corneal cells in response to inflammation, and reduction of inflammation with non-steroidal anti-inflammatory drugs. Primary cultures of human conjunctival epithelial cells, fibroblasts, corneal epithelial cells, and keratocytes were incubated with IL-4 and TNF-α. PGE2 and COX-2 levels were analyzed. Effects of anti-inflammatory and anti-immune drugs on PGE2 production were also investigated. IL-4 and TNF-α induced the generation of PGE2 and COX-2 in conjunctival and corneal cells. Epithelial PGE2 production was significantly lower than in keratocytes and fibroblasts, which was down-regulated by aspirin. IL-4 and TNF-α enhanced the inflammatory response via prostaglandin production which contributed to ocular surface inflammation. Prostaglandin production was higher in stromal cells than epithelial cells. These results suggest that the epithelial barrier disruption may contribute to ocular allergic inflammation by the PGE2 production from stromal cells. Moreover, NSAIDs were effective in suppressing PGE2 production in our experiment.

Aetiology-specific comparison of long-term outcome of deep anterior lamellar keratoplasty for corneal diseases.

AIMS: To evaluate the long-term outcome of deep anterior lamellar keratoplasty (DALK) for the treatment of herpetic keratitis, keratoconus, stromal scars and corneal dystrophies. METHODS: This retrospective consecutive case study includes 275 consecutive eyes of 254 patients who underwent DALK; 35 eyes with herpetic keratitis, 114 eyes with stromal scar, 93 eyes with keratoconus and 67 eyes with corneal dystrophy. Exclusion criteria included therapeutic DALK for the treatment of descemetocele or infectious keratitis, and eyes with limbal stem cell deficiency. Patients were examined at 1, 3 and 6 months, and 1, 3 and 5 years after DALK. Graft survival rate, best corrected visual acuity (BCVA), endothelial cell density (ECD) and postoperative complications were evaluated. RESULTS: The mean postoperative follow-up duration was 51±41 months. The graft survival rate of all subjects was 96.8% at 1 year, 89.9% at 3 years, 83.5% at 5 years and 74.1% at 10 years. At 6 months, BCVA significantly improved from 1.14±0.54 to 0.22±0.21 in the keratoconus group, from 1.13±0.60 to 0.44±0.54 in the herpes group, from 1.00±0.59 to 0.49±0.38 in the stromal scar group and from 1.04±0.52 to 0.32±0.29 in the corneal dystrophy group (all, p<0.0001). BCVA stabilised after 6 months thereafter up to 5 years. ECD decreased just after DALK and maintained >1000 cell/mm(2) at 5 years in all groups. CONCLUSIONS: DALK provides good visual acuity with slight ECD decrease over long term in all groups.

Efficacy of bromfenac sodium ophthalmic solution for treatment of dry eye disease.

PURPOSE: To evaluate the efficacy of bromfenac sodium ophthalmic solution (BF) in patients with dry eye disease (DED) inadequately controlled by monotherapy with artificial tears (ATs). DESIGN: An investigator-oriented trial with a single-arm, nonrandomized, open-label design. METHODS: Twenty-six patients, who showed no symptomatic improvement of DED after 1 month of AT treatment, were enrolled. Bromfenac sodium ophthalmic solution was administered adjunctively with AT for 1 month. The BF treatment was then discontinued, and AT treatment alone was continued for 3 months. The signs and symptoms were evaluated at the beginning of BF treatment (Pre), at the end of the combined BF and AT treatment (BF1M), and at 1 and 3 months after discontinuation of BF treatment (Po1M and Po3M, respectively). RESULTS: The dryness scores at BF1M were significantly improved compared with Pre (P < 0.001) and significantly superior to Po3M (P < 0.001). No significant changes in the Schirmer scores were observed throughout the treatment period. The tear film breakup time was significantly improved at BF1M (4.4 ± 2.3 seconds) compared with Pre (2.8 ± 1.8 seconds; P < 0.001). Superficial punctate keratopathy showed significant improvements in the total score of area and density at BF1M compared with Pre (P < 0.001). However, these parameters had significantly worsened at Po3M compared with BF1M. No adverse events were observed. CONCLUSIONS: Bromfenac sodium ophthalmic solution has improved the dryness of the eye and signs of DED through its anti-inflammatory effects. Nonsteroidal anti-inflammatory drugs were suitable as anti-inflammatory ophthalmic solutions for patients with DED.

Efficacy of a novel moist cool air device in office workers with dry eye disease.

PURPOSE: To evaluate the efficacy and safety of new moist cool air device (MCAD) for ocular symptoms, tear film stability and ocular surface status in office workers with dry eye disease (DED). METHODS: In this prospective single-centre clinical trial, 40 eyes of 20 patients with DED were recruited and randomly divided into two groups (group with MCAD exposure and group without MCAD). All subjects are visual display terminals (VDTs) workers spending at least 4 h/day in front of VDTs. Patients using MCAD underwent moist air applications for 4 h/day for a total of five working weekdays during VDT works at their offices. The other group of patients performed their VDT work without moist cool air device exposure. The change in symptoms of ocular surface (OS) dryness, fatigue and discomfort was evaluated using visual analogue scale (VAS) scores. Changes in visual function, tear functions and ocular surface status were evaluated using best-corrected visual acuity (BCVA), the functional visual acuity (FVA) test, blink rate, BUT measurements, strip meniscometry (SM), tear evaporation rate, fluorescein staining and rose bengal staining scores. Tear film lipid layer interferometry was also performed to assess the status of the lipid layer over the tear film. In addition, adverse events were recorded. RESULTS: In group with MCAD, symptoms of OS dryness during VDTs work, and FVA and BUT were significantly improved. SM and tear evaporation rate were significantly improved. There were no statistically significant differences on lipid layer stability and corneal staining scores in both groups. Blink rate was significantly increased in group without MCAD. No adverse events were reported during this trial. CONCLUSION: Moist cool air device use provided symptomatic relief of ocular dryness and improvement on tear stability in office workers with DED. This new device seems to be a safe and promising alternative in the treatment of DED.

Intraocular pressure elevation after Descemet's stripping endothelial keratoplasty.

PURPOSE: To investigate the incidence of intraocular pressure (IOP) elevation after Descemet's stripping endothelial keratoplasty (DSEK) and associated clinical findings. METHODS: Forty-eight eyes of 46 patients who underwent DSEK were studied in this single-center retrospective study. IOP elevation was defined as the presence of an increase in IOP above 21 mmHg lasting at least two months, the need to introduce topical/oral antiglaucoma medications for at least two months, and the need for surgical therapy for uncontrolled IOP. Patients with pre-existing glaucoma or patients who were using antiglaucoma drugs before DSEK were excluded according to the protocol of the study. The incidence of post-DSEK IOP elevation was investigated. RESULTS: The incidence of IOP elevation after DSEK was 16.7 %. Glaucoma therapy following DSEK was needed in eight eyes of eight patients. IOP elevations were diagnosed from two to ten months after DSEK. There was no statistical difference in the survival probabilities of patients with different preoperative diagnoses. Pre-op IOP was observed to be a risk factor of IOP elevation in this series. CONCLUSIONS: IOP elevation appears to be a common postoperative complication of DSEK. Patients without preexisting glaucoma but with higher pre-op IOP need to be followed up carefully after DSEK.

The comparison of solitary topical micafungin or fluconazole application in the treatment of Candida fungal keratitis.

AIM: To compare and evaluate the efficacy of topical 0.1% micafungin (MCFG) and topical 0.2% fluconazole (FCZ) in the treatment of Candida fungal keratitis. METHODS: Twenty-nine eyes of 29 patients who were diagnosed as having Candida fungal keratitis, proven by corneal culture isolates, were investigated in this prospective study. Patients were divided into a MCFG treatment group (12 eyes) and an FCZ treatment group (17 eyes). Age, gender, initial status of ulcer (ulcer size and degree of injection), initial and final best-corrected visual acuity (BCVA), healing periods, final status of cornea and recurrences in each group were studied and compared. RESULTS: There were no significant differences in relation to age, gender, ulcer size and degree of injection before treatment between the two groups. There were also no significant differences in the healing periods until complete epithelialisation (MCFG treatment group (41.3 ± 38.0 days); FCZ treatment group (34.4 ± 37.7 days)), change in BCVA, corneal clarity/opacification, perforation and recurrence status at the final examination between the two groups. CONCLUSION: The efficacy of 0.1% MCFG eye-drops appears to be comparable with that of 0.2% FCZ eye-drops in the treatment of Candida fungal keratitis.

Increased serum total antioxidant status and decreased urinary 8-hydroxy-2'-deoxyguanosine levels in patients with normal-tension glaucoma.

PURPOSE: To investigate the amount of systemic oxidative stress-related DNA damage and serum total antioxidant status of patients with normal-tension glaucoma compared with healthy controls. METHODS: Forty-three patients with normal-tension glaucoma selected from 60 consecutive newly diagnosed patients with primary open-angle glaucoma were enrolled. Each patient's intraocular pressure (IOP) was measured seven times over a 24-hour period. Those whose highest IOP was over 21 mmHg were excluded. Forty control subjects were recruited. The serum total antioxidant status was assessed colorimetrically by its ability to reduce the generation of the radical cation ABTS (2,2-azinobis-3-ethylbenzthiazoline sulphonate). The urinary 8-hydroxy-2'-deoxyguanosine was measured as a marker of oxidative DNA damage and normalized to creatinine. The results were compared between healthy subjects and patients with normal-tension glaucoma. RESULTS: The control and normal-tension glaucoma groups did now show significant differences for age, gender, serum fructosamine, cholesterol and triglyceride levels; systolic and diastolic blood pressure, body mass index; and prevalence of hypertension. The serum total antioxidant status was significantly higher (p = 0.01) and the urinary 8-hydroxy-2'-deoxyguanosine/creatinine level significantly lower (p = 0.03) in the patients with normal-tension glaucoma compared with the controls. Even after we adjusted the data for independent variables, the incidence of normal-tension glaucoma was significantly correlated with high serum total antioxidant levels (p = 0.03; odds ratio, 1.007; 95% confidence interval, 1.001-1.013) and low urinary 8-hydroxy-2'-deoxyguanosine/creatinine (p = 0.02; odds ratio 0.76; 95% confidence interval, 0.61-0.96). CONCLUSIONS: Increased serum total antioxidant and decreased 8-hydroxy-2'-deoxyguanosine may reflect compensatory alterations in response to increased systemic oxidative stress in patients with normal-tension glaucoma.

Calorie restriction: A new therapeutic intervention for age-related dry eye disease in rats.

A decrease in lacrimal gland secretory function is closely related to aging and leads to an increased prevalence of dry eye syndrome. Since calorie restriction (CR) is considered to prevent functional decline of various organs due to aging, we hypothesized that CR could prevent age-related lacrimal dysfunction. Six-month-old male Fischer 344 rats were randomly divided into ad libitum (AL) and CR (-35%) groups. After 6months of CR, tear function was examined under conscious state. After euthanasia, lacrimal glands were subjected to histological examination, tear protein secretion stimulation test with Carbachol, and assessment of oxidative stress with 8-hydroxy-2 deoxyguanosine (8-OHdG) and 4-hydroxynonenal (HNE) antibodies. CR significantly improved tear volume and tended to increase tear protein secretion volume after stimulation with Carbachol compared to AL. The acinar unit density was significantly higher in the CR rats compared to AL rats. Lacrimal glands in the CR rats showed a lesser degree of interstitial fibrosis. CR reduced the concentration of 8-OHdG and the extent of staining with HNE in the lacrimal gland, compared to AL. Furthermore, our electron microscopic observations showed that mitochondrial structure of the lacrimal gland obtained from the middle-aged CR rats was preserved in comparison to the AL rats. Collectively, these results demonstrate for the first time that CR may attenuate oxidative stress related damage in the lacrimal gland with preservation of lacrimal gland functions. Although molecular mechanism(s) by which CR maintains lacrimal gland function remains to be resolved, CR might provide a novel therapeutic strategy for treating dry eye syndrome.

Pupillary Block Glaucoma After Implantation of Iris-Fixated Phakic Intraocular Lens.

To report a case of pupillary block glaucoma after implantation of iris-fixated phakic intraocular lens (IF pIOL). A 43-year-old man was referred for pupillary block one day after implantation of IF pIOL. Slit-lamp examination revealed extremely shallow anterior chamber, closure of peripheral laser iridotomy and contact of iris on the peripheral of the optics of IF pIOL. The intraocular pressure (IOP) was 62 mm Hg. The iris moved forward in contact with the IF pIOL and the lens remained in the physiologic position, which made the distance between the lens and the iris wide. He underwent an uneventful peripheral surgical iridectomy and the IOP decreased to 6 mm Hg. Acute pupillary block glaucoma can occur after IF pIOL implantation due to the occlusion of aqueous flow between the IF pIOL and the iris if the peripheral iridotomy closes.

Reduced-serum vitamin C and increased uric acid levels in normal-tension glaucoma.

BACKGROUND: Vitamin A, B(9), C, E, and uric acid are well-known antioxidants and may prevent age-related eye disorders. The aim of the present study was to investigate the levels of antioxidant vitamins, A, B(9), C, E, and antioxidative substance, uric acid in the serum of Japanese patients with normal-tension glaucoma and compare the results with normal controls. METHODS: All subjects with suspicion of primary open-angle glaucoma who came to the glaucoma subspeciality clinic of Keio University Hospital were enrolled in this study. Sixty patients (28 males, 32 females; mean age +/- standard deviation: 59.9 +/- 9.8 years) with newly diagnosed primary open-angle glaucoma patients were consecutively enrolled in this study. After the diagnosis of primary open-angle glaucoma, the patients underwent 24-h IOP measurements. Forty-seven newly diagnosed consecutive normal-tension glaucoma patients (18 males, 29 females; mean age +/- standard deviation: 59.5 +/- 10.2 years) were enrolled in this study. The control subjects were recruited from subjects who came to the clinic for annual refractive check-up. The 44 consecutive control subjects of the current study, (16 males, 28 females; 62.7 +/- 14.8 years) did not have any ocular diseases. The serum levels of vitamins A, B(9), C, E, and uric acid were measured. The values were compared between the normal-tension glaucoma and control groups by the Mann-Whitney U test. RESULTS: Serum levels of vitamin C were significantly lower in normal-tension glaucoma patients than in normal healthy controls (P = 0.04; normal-tension glaucoma; 4.6 +/- 4.0 microg/ml control; 6.3 +/- 3.9 microg/ml). Uric acid level was significantly higher in normal-tension glaucoma patients than in controls (P = 0.01; normal-tension glaucoma; 5.8 +/- 1.5 mg/dl control; 4.9 +/- 1.4 mg/dl). No statistically significant difference was seen in vitamin A (P = 0.41; normal-tension glaucoma; 82.1 +/- 26.7 microg/dl control; 77.1 +/- 30.1 microg/dl), B(9) (P = 0.37; normal-tension glaucoma; 8.7 +/- 4.3 ng/ml control; 8.0 +/- 3.1 ng/ml)and E (P = 0.83; normal-tension glaucoma; 1.5 +/- 0.6 control; 1.5 +/- 0.6) levels between normal-tension glaucoma and control groups. CONCLUSION: Normal-tension glaucoma patients had lower serum levels of vitamin C and increased levels of uric acid. These observations may pave the way for possible alternative treatment for normal-tension glaucoma.

Effect of anterior and posterior corneal surface irregularity on vision after Descemet-stripping endothelial keratoplasty.

PURPOSE: To evaluate irregularity of the anterior and posterior cornea before and after Descemet-stripping endothelial keratoplasty (DSEK) and its effect on visual acuity. SETTING: Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan. METHODS: Corneal data were acquired using a rotating Scheimpflug camera before and 1 month and 3 months after DSEK. Anterior and posterior corneal elevation data were decomposed into a set of Zernike polynomials up to the 8th order within a 4.0 mm diameter region. Total higher-order root mean square (HO-RMS) and RMS from the 3rd to 8th order were calculated. The effects of anterior and posterior surface irregularity on visual acuity were evaluated. RESULTS: This clinical study comprised 13 consecutive eyes of 12 bullous keratopathy patients. The mean best corrected visual acuity (BCVA) was 1.11 logMAR +/- 0.5 (SD) preoperatively, 0.49 +/- 0.49 logMAR 1 month postoperatively, and 0.27 +/- 0.32 logMAR at 3 months. The HO-RMS of the anterior surface 1 month (P = .040) and 3 months (P = .048) postoperatively was significantly lower than preoperatively. There were no significant differences in posterior surface HO-RMS between preoperatively and 1 month (P = .45) and 3 months (P = .054). The postoperative BCVA was significantly correlated with HO-RMS (P<.001), but not with posterior surface HO-RMS, at 3 months (P = .354). CONCLUSION: Postoperative BCVA correlated with irregularity of the anterior surface but not the posterior surface. In addition to corneal transparency, regularity of the anterior surface is an important factor in visual acuity after DSEK.

Diagnosis of steroid-induced glaucoma after photorefractive keratectomy.

PURPOSE: To report steroid-induced glaucoma after photorefractive keratectomy (PRK). METHODS: A 50-year-old Japanese woman was referred for endstage glaucoma 9 months after PRK. Topical fluorometholone 0.1% was administered for corneal subepithelial haze in both eyes for 9 months after PRK. Pneumatic non-contact tonometry values of intraocular pressure (IOP) remained normal (range: 11 to 17 mmHg), until she was diagnosed with end-stage steroid-induced glaucoma with extensive restriction in visual fields. At the patient's initial examination in our hospital, IOP measured by Goldmann applanation tonometry was 34 mmHg in the right eye and 32 mmHg in the left eye, but the estimated IOP as corrected by central corneal thickness measurement was >40 mmHg in both eyes. RESULTS: The patient underwent uneventful bilateral trabeculectomies, resulting in reduction of IOP to <10 mmHg in both eyes. CONCLUSIONS: The underestimation of IOP after PRK led to advanced visual field loss. Careful evaluation of IOP, optic disc, and visual field tests are indispensable to avoid such a devastating outcome after PRK.