Tomoyuki Kashima

Rebamipide ophthalmic suspension for the treatment of dry eye syndrome: a critical appraisal

Rebamipide was initially developed and approved for use in treating gastric ulcers and lesions associated with gastritis. Discovery of its ability to increase gastric mucin led to investigations of its effect on ocular surface mucin and the subsequent development for use in dry eye patients. Investigations have confirmed that rebamipide increases corneal and conjunctival mucin-like substances along with improving corneal and conjunctival injury. Clinically, rebamipide ophthalmic suspensions can effectively treat tear deficiency and mucin-caused corneal epithelial damage, and can restore the microstructure responsible for tear stability. Topical rebamipide has also been shown to be effective in treating other ocular surface disorders such as lagophthalmos, lid wiper epitheliopathy, and persistent corneal erosion. Rebamipide’s ability to modify epithelial cell function, improve tear stability, and suppress inflammation in the absence of any known major side effects suggest that it may be a beneficial first drug of choice for severe dry eye treatment and other ocular surface disorders. This review summarizes the history and development of this innovative dry eye treatment from its initial use as an effective stomach medication to its current use in the treatment of dry eye in Japan.

Retinal Ganglion Cell Analysis in Leber's Hereditary Optic Neuropathy

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Resolution of persistent corneal erosion after administration of topical rebamipide

Rebamipide is an antiulcer agent used to treat gastric ulcer and gastritis. Biological effects of rebamipide include cytoprotection, wound healing, and anti-inflammatory properties that are known to be universal for a variety of tissues in addition to gastrointestinal mucosa. The therapeutic effects of rebamipide eye drops are due to its ability to increase corneal and conjunctival mucin-like substances and improve corneal and conjunctival injury in vivo. In this paper, we report a case of Sjögren’s syndrome with complete disappearance of corneal erosion after administration of rebamipide eye drops. This was observed even though corneal erosion had not improved for 6 months after punctal occlusion surgery. The patient was a 33-year-old female, diagnosed with Sjögren’s syndrome by a salivary gland biopsy. The corneal and conjunctival surfaces were filled with dense erosions, which did not improve with topical drugs. Punctal plugs were applied several times; however, the plugs were repeatedly shed. All four puncta of both eyelids were surgically occluded, and both corneal and conjunctival erosion was clearly improved. However, the erosion in the inferior cornea of both eyes had not improved for 6 months after surgery. We used the newly approved topical rebamipide for treatment of this patient. The corneal erosion gradually improved and completely disappeared 4 weeks after administration of the drug. Dry eye sensation disappeared at the same time. Both membrane-associated mucin and secreted mucin in the ocular surface are thought to be essential for maintenance of the tear film. Induction of mucin from ocular surface epithelium could be an effective treatment in cases of dry eye caused by mucin deficiency. Through its various mechanisms, rebamipide improves ocular surface conditions. To our knowledge, this is the first clinical case report using rebamipide ophthalmic solution. This drug may provide a novel approach to treat drying diseases of the eye.

Topical rebamipide improves lid wiper epitheliopathy

Administration of topical rebamipide increases the mucin level of tear film and improves the ocular surface in short break-up time type of dry eye. Lid wiper epitheliopathy (LWE) is a disorder of the marginal conjunctiva of the upper eyelid with dry eye symptoms. LWE may be related to mechanical forces during blinking resulting in inflammation of the ocular surface. Rebamipide also has various anti-inflammatory effects. In this report, we tried treatment with topical rebamipide for two cases of LWE. One case had been treated with sodium hyaluronate ophthalmic solution and diquafosol sodium eye drops by other doctors for several weeks. The other case was not previously treated. In both cases, fluorescein staining of the cornea and lid margin was remarkably improved, ocular symptoms decreased, and tear film break-up times increased with rebamipide eye drops four times daily for 2-3 weeks. Topical rebamipide was effective for corneal and conjunctival disorders in LWE. This drug may provide a novel approach to the treatment of LWE.

Longitudinal Tear of the Inferior Rectus Muscle in Orbital Floor Fracture

We report a case of longitudinal avulsion of the inferior rectus muscle following orbital floor fracture and describe its clinical presentation, computed tomography (CT) features and management. A 53-year-old man felt vertical diplopia in all gaze immediately after the trauma. Orthoptic assessment showed left over right hypertropia of 20 prism diopters and left exotropia of 10 prism diopters in primary position. The left orbital floor fracture and the prolapse of orbital contents into the maxillary sinus were presented by CT. Exploration of the orbit was performed under general anesthesia. The displaced bone fragment was elevated and repositioned below the slastic implant. Diplopia continued in all directions of gaze, although the impairment of depression was reduced postoperatively. A residual left hypertropia of 10 prism diopters and exotropia of 10 prism diopters was present in primary position 1 month after surgery, though there were no enopthalmos or worsening of hypesthesia. Repeated CT revealed the muscle avulsion of inferior rectus at the lateral portion of the belly. The avulsion of a small segment of the inferior rectus and its herniation into maxillary sinus in more posterior views was detected by review of the preoperative images. Muscle avulsion should be considered in the management of orbital fracture if orbital tissue entrapment and nerve paresis are excluded as causes of reduction in ocular motility. A thorough review of the imaging studies for possible muscle injury is required before surgery in all cases of orbital fracture.

Intravitreal gas injection without vitrectomy for macular detachment associated with an optic disk pit.

Purpose: To evaluate the clinical outcomes after gas tamponade without vitrectomy for retinal detachment associated with an optic disk pit using optical coherence tomography. Methods: Intravitreal gas injection was performed on 8 consecutive patients (mean age, 35.0 years; range, 15–74 years) with unilateral macular detachment associated with an optic disk pit. A 0.3-mL injection of 100% sulfur hexafluoride 6 gas was carried out without an anterior chamber tap. Patients treated with gas injection were instructed to remain facedown for 5 days. Results: Complete retinal reattachment after only gas tamponade was achieved in four out of eight eyes. The mean number of gas injections was 1.8. The mean best-corrected visual acuity before and after the treatment with gas tamponade was approximately 30/100 and 20/20, respectively. The period required for reattachment after final gas treatment was 12 months. There were no incidences of recurrence after complete reattachment by gas tamponade in any of the cases during the 94-month average follow-up period (range, 64–132 months). Conclusion: Gas tamponade appears to be an effective alternative method for macular detachment associated with an optic disk pit, even though the mechanisms of optic disk pit maculopathy are still unknown.

Bulbar conjunctival sporotrichosis presenting as a salmon-pink tumor.

Purpose: To report a patient with bulbar conjunctival sporotrichosis presenting as a salmon-pink tumor. Methods: This was an interventional case report. A 62-year-old woman presented with conjunctival injection in her left eye. Despite administration of topical dexamethasone sodium, ofloxacin, and levocabastine hydrochloride, her symptoms failed to improve and she was referred to us. Results: Four weeks after referral to us, the patient gradually developed conjunctival injection in both eyes and a salmon-pink tumor in the bulbar conjunctiva of the left eye. Excision biopsy was performed and pathologic examination revealed an epithelioid granuloma with microabscesses and infiltration of plasma cells with yeast-like spherules. A sporotrichin intradermal test was strongly positive. Based on a diagnosis of sporotrichosis, we treated her with topical fluconazole 0.2% in both eyes and oral potassium iodide (450 mg). The bilateral conjunctival injection and subconjunctival tumor in the left eye gradually resolved and had completely disappeared after 3 months of treatment. Conclusion: This is the first report of bulbar conjunctival sporotrichosis with a salmon-pink conjunctival tumor. Although rare, ophthalmologists should be aware of this entity during examination of patients with intractable conjunctival injection.

Massive macular hard exudates associated with branch retinal vein occlusion.

PurposeTo report four cases of branch retinal vein occlusion (BRVO) with the complication of serous retinal detachment (SRD).MethodsWe retrospectively studied four eyes of four patients with macular edema and macular hard exudates associated with midperipheral BRVO. Visual acuity, ophthalmoscopy, fluorescein angiography, and optical coherence tomography findings were evaluated. Three of the four eyes underwent laser photocoagulation in the BRVO area 1 month after the initial visit.ResultsMacular edema consisted of SRD without cystoid macular edema in all eyes. Late-phase fluorescein angiography showed extensive dye leakage in the BRVO area. When SRD was resolved 4 months after the initial examination, hard exudates had increased in the macular area. Although macular hard exudates decreased 1 year after the initial examination, visual acuity remained under 20/20 because of macular atrophy.ConclusionsSRD is one type of macular edema observed in BRVO. In macula-spared midperipheral BRVO, the SRD originates from a vascular leaking area, and there is a high risk that massive macular hard exudates will develop, which may affect visual recovery. Jpn J Ophthalmol 2005;49:527–529© Japanese Ophthalmological Society 2005

Topical rebamipide improves the ocular surface in mild lagophthalmos

Administration of topical rebamipide improves the ocular surface in dry eye. We consecutively studied seven eyes in seven cases (three males and four females) with mild lagophthalmos (three cases after eyelid surgery, two cases of incomplete facial nerve palsy, and two cases of senile ectropion) during the treatment of corneal disorders with rebamipide eye drops four times daily for 2 weeks. The fluorescein corneal staining (FCS) score, tear film break-up time (TBUT), Schirmer’s test, and decimal visual acuity were examined. Ocular symptoms were examined and scored by questioning each patient before and after administration of the drug. In all seven eyes, inferior corneal erosion decreased or disappeared within 2 weeks after administration of topical rebamipide. The FCS score was significantly improved (P < 0.05). The TBUT was significantly extended from 2.9 ± 0.5 seconds to 5.2 ± 0.4 seconds (P < 0.05). The scores of ocular symptoms, such as eye pain, dryness, blurred vision, and foreign body sensations, were significantly improved (P < 0.05).Topical rebamipide was effective for corneal disorders in mild lagophthalmos. This drug may provide a novel approach to treat lagophthalmos.

Improved subjective symptoms of conjunctivochalasis using bipolar diathermy method for conjunctival shrinkage

Purpose To evaluate the improvement in subjective symptoms of conjunctivochalasis after bipolar coagulation. Methods Forty-three eyes of 26 patients (average age, 75.7 ± 8.4 years) were included in this study. The inferior conjunctivas were cauterized between April 2009 and June 2010. Surgery involved pinching the excess conjunctiva and performing bipolar cauterization after subconjunctival injection of a local anesthetic agent. Patients were asked to describe the postoperative foreign-body sensation and change in subjective symptoms 1 month postoperatively, with the preoperative symptom score defined as 10. Results Twenty-two patients (84.6%) reported symptom relief immediately after the procedure, though all patients had a mild gritty sensation for 1–2 weeks postoperatively. The mean postoperative symptom score obtained from the questionnaire was 3.27 ± 3.31, which was significantly lower than the preoperative score (P < 0.0001). No patients had experienced recurrent symptoms at the end of the follow-up period. Conclusion Thermal cauterization can achieve conjunctival shrinkage and adherence to the subconjunctival tissues. Operation time is only a few minutes, postoperative pain is not severe, and the procedure can be performed in an outpatient clinic, all of which represent benefits to the patients.