Efficacy of Rebamipide Instillation for Contact Lens Discomfort With Dry Eye.

OBJECTIVE: To examine the effects of rebamipide ophthalmic solution on the symptoms, signs, and cytokine concentrations in tear fluid among soft contact lens (SCL) wearers with Dry eye disease (DED). METHODS: From November 2015 to June 2017, this open-label, single-arm study examined 40 eyes of 20 SCL wearers with DED who had been using daily disposable SCLs for >3 months (mean age, 30.0±8.33 years; range, 20-47 years). Signs, symptoms, and cytokine concentrations were assessed before and 4 weeks after starting 2% rebamipide ophthalmic solution 4 times/day. Dry eye disease was diagnosed according to: compromised tear dynamics (Schirmer test ≤5 mm or tear break-up time (TBUT) ≤5 sec); ocular surface abnormalities (positive vital staining with fluorescein or lissamine green); and presence of symptoms. Touch thresholds using a Cochet-Bonnet anesthesiometer were also determined for the cornea and conjunctivae. Symptoms were assessed using the 12-item Ocular Surface Disease Index questionnaire. Concentrations of cytokines in tear fluid were measured. RESULTS: Significant improvements in signs were seen for TBUT, surface abnormalities, and touch thresholds. Ocular Surface Disease Index scores likewise improved significantly in all the 12 items. Of the cytokines measured, only interleukin-1ß, interleukin-8, and monocyte chemotactic protein-1 were found in ≥60% of tear samples, with no significant differences in concentrations before and after rebamipide use. CONCLUSIONS: Rebamipide significantly improved all signs and symptoms in patients with DED who wore daily disposable SCLs. Rebamipide is effective for DED treatment with SCL wear.

Improved Intravitreal AAV-Mediated Inner Retinal Gene Transduction after Surgical Internal Limiting Membrane Peeling in Cynomolgus Monkeys.

The retina is an ideal target for gene therapy because of its easy accessibility and limited immunological response. We previously reported that intravitreally injected adeno-associated virus (AAV) vector transduced the inner retina with high efficiency in a rodent model. In large animals, however, the efficiency of retinal transduction was low, because the vitreous and internal limiting membrane (ILM) acted as barriers to transduction. To overcome these barriers in cynomolgus monkeys, we performed vitrectomy (VIT) and ILM peeling before AAV vector injection. Following intravitreal injection of 50 µL triple-mutated self-complementary AAV serotype 2 vector encoding EGFP, transduction efficiency was analyzed. Little expression of GFP was detected in the control and VIT groups, but in the VIT+ILM group, strong GFP expression was detected within the peeled ILM area. To detect potential adverse effects, we monitored the retinas using color fundus photography, optical coherence tomography, and electroretinography. No serious side effects associated with the pretreatment were observed. These results indicate that surgical ILM peeling before AAV vector administration would be safe and useful for efficient transduction of the nonhuman primate retina and provide therapeutic benefits for the treatment of retinal diseases.

[Ophthalmoplegia without severe painful eyelid swelling in acute dacryoadenitis: a case report].

Here, we present a case of right eyelid drooping in a 79-year-old man. Neurological examination revealed ptosis of the right eye without severe painful eyelid swelling and redness. An ocular motility examination of the right eye revealed upward limitation and downward overshoot. The results of routine blood examinations were within normal limits, and no autoantibodies were detected. Orbital magnetic resonance images revealed mild right eyelid swelling and lacrimal gland enlargement, indicating orbital inflammation. The ocular discharge was positive for Staphylococcus hominis by culture and the patient was diagnosed as having acute dacryoadenitis. Treatment with topical and systemic administration of antibiotics rapidly improved symptoms. Ocular infection is not usually suspected in the absence of local severe painful swelling and redness, and painless acute dacryoadenitis presenting as ophthalmoplegia and ptosis may be misdiagnosed. Orbital inflammation may rapidly progress to orbital cellulitis with treatment delay, which may also lead to aggravation of ophthalmic prognosis. Therefore, neurologists should be aware of the possibility of acute dacryoadenitis occurring without the local severe inflammatory findings mimicking neurological diseases, and acute dacryoadenitis should be considered in patients with ophthalmoplegia even in the absence of severe painful eyelid swelling and redness.

Adeno-associated virus type 8 vector-mediated expression of siRNA targeting vascular endothelial growth factor efficiently inhibits neovascularization in a murine choroidal neovascularization model.

PURPOSE: To assess the feasibility of a gene therapeutic approach to treating choroidal neovascularization (CNV), we generated an adeno-associated virus type 8 vector (AAV2/8) encoding an siRNA targeting vascular endothelial growth factor (VEGF), and determined the AAV2/8 vector's ability to inhibit angiogenesis. METHODS: We initially transfected 3T3 cells expressing VEGF with the AAV2/8 plasmid vector psiRNA-VEGF using the H1 promoter and found that VEGF expression was significantly diminished in the transfectants. We next injected 1 µl (3 × 10(14) vg/ml) of AAV2/8 vector encoding siRNA targeting VEGF (AAV2/8/SmVEGF-2; n = 12) or control vector encoding green fluorescent protein (GFP) (AAV2/8/GFP; n = 14) into the subretinal space in C57BL/6 mice. One week later, CNV was induced by using a diode laser to make four separate choroidal burns around the optic nerve in each eye. After an additional 2 weeks, the eyes were removed for flat mount analysis of the CNV surface area. RESULTS: Subretinal delivery of AAV2/8/SmVEGF-2 significantly diminished CNV at the laser lesions, compared to AAV8/GFP (1597.3 ± 2077.2 versus 5039.5 ± 4055.9 µm(2); p<0.05). Using an enzyme-linked immunosorbent assay, we found that VEGF levels were reduced by approximately half in the AAV2/8/SmVEGF-2 treated eyes. CONCLUSIONS: These results suggest that siRNA-VEGF can be expressed across the retina and that long-term suppression of CNV is possible through the use of stable AAV2/8-mediated siRNA-VEGF expression. In vivo gene therapy may thus be a feasible approach to the clinical management of CNV in conditions such as age-related macular degeneration.

Detection of Streptococcus species by polymerase chain reaction in infectious crystalline keratopathy.

PURPOSE: Investigation of a positive polymerase chain reaction (PCR) for Streptococcus species from an excised cornea of a patient with infectious crystalline keratopathy. METHODS: Samples microdissected from corneal intrastromal aggregates present in infectious crystalline keratopathy were subjected to PCR for 3 primer pairs respectively specific for Streptococcus, Staphylococcus, and several kinds of fungi. RESULTS: The PCR detected DNA from Streptococcus but not from Staphylococcus or fungi. Direct sequencing of the PCR products showed that the PCR products had the highest identity (99.8%) with Streptococcus mitis and Streptococcus gordoni, indicating that these species were the most probable causes of infectious crystalline keratopathy in this patient. CONCLUSION: Our findings suggest that PCR provides a good adjunct technique in the diagnosis of corneal infection.

[Angle-closure glaucoma: important points in the diagnosis and follow-up].

A 74-year-old woman visited her local physician complaining of fever, cough, headache, hyperemic left conjunctiva, and blurred vision. She was diagnosed as having common cold and medicated for it, and later, she visited our department. She had a shallow left anterior chamber with moderately dilated pupil. Gonioscopic examination of the left eye revealed a narrow angle corresponding to grade 1 by Shaffer grading system. Left intraocular pressure was 16 mmHg. She was diagnosed to have had a spontaneous recovery from a subacute attack of angle-closure glaucoma. Laser iridectomy was performed and she was put on a regular ophthalmological follow-up. Three years later, she experienced an attack of left angle-closure glaucoma secondary to lens intumescence. She was treated by phacoemulsification and aspitaion which resulted in the eventual cure.