5-Fluorouracil in primary, impending recurrent and recurrent pterygium: Systematic review of the efficacy and safety of a surgical adjuvant and intralesional antimetabolite.

Pterygium is an ultraviolet-related disease characterized by an aberrant, wing-shaped and active wound-healing process. There is nothing quite as disheartening for the surgeon or patient as the recurrence of pterygium, and various adjuvants have been studied to ameliorate this. This systematic review provides a comprehensive summary of the efficacy and safety of 5-Fluorouracil (5-FU) as an antimetabolite agent for pterygium management. An appraisal of electronic searches of six databases identified 34 clinical studies reporting recurrence outcomes of 5-FU use in primary, impending recurrent and recurrent pterygia. In vitro and in vivo studies of 5-FU showed dose- and duration-dependent cytostatic and cytotoxic effects in human cells. 5-FU is relatively inexpensive, available, and easy to administer, making it attractive for resource-limited scenarios. However, the published evidence demonstrates a recurrence rate of 11.4-60% with the bare scleral technique, 3.5-35.8% with conjunctival rotational flaps, 3.7-9.6% with conjunctival autografts for intraoperative topical 5-FU, and 14-35.8% for preoperative and intraoperative injections. This suboptimal efficacy brings the role of 5-FU as an adjuvant for pterygium surgery into question and the authors do not recommend its use. In contrast, postoperative intralesional injections of 5-FU to arrest progression in impending recurrent pterygium and true recurrent pterygia were more promising, with success rates of 87.2-100% and 75-100%, respectively. Furthermore, 5-FU as a treatment modality, without surgery, effectively arrested progression in 81.3-96% of primary and recurrent pterygia. Other treatments such as topical and intralesional corticosteroids, cyclosporine and anti-VEGF agents are discussed. Complications of 5-FU increase with higher doses and range from transient and reversible to severe and sight-threatening. For pterygium, 5-FU has a predilection for causing scleral thinning, corneal toxicity, and graft-related complications. Additional study with extended follow-up is needed to elucidate the optimal dose, frequency, duration, and long-term safety of 5-FU injections. If 5-FU is used in the management of pterygium, it should be with caution, in selected patients and with vigilant long-term monitoring.

Corneal Effects of Tea Tree Oil.

PURPOSE: The purpose of this study is to report a case of corneal epithelial defects resulting from topical treatment of blepharitis with tea tree oil (TTO). METHODS: A 44-year-old man with a 1 year history of blepharitis non-responsive to eyelid hygiene was found to have signs of Demodex infestation. He was treated with a topical, off-label 50% TTO solution. Shortly afterward, the patient complained of bilateral ocular discomfort. RESULTS: Slit-lamp examination revealed conjunctival injection and a corneal epithelial defect in both eyes. Treatment with lubricant, antibiotic, and steroid eye drops as well as bandage contact lenses was required to facilitate corneal healing. CONCLUSIONS: Topical use of off-label, 50% concentration TTO can result in corneal epithelial defects. Eye care professionals should remain aware of this risk and only use approved, low-concentration TTO products when treating Demodex-related blepharitis.

Randomized, Controlled, Double-Masked, Multicenter, Pilot Study Evaluating Safety and Efficacy of Intranasal Neurostimulation for Dry Eye Disease.

Purpose: We assess the safety and effectiveness of intranasal neurostimulation to promote tear production via the nasolacrimal pathway in subjects with dry eye disease. Methods: A multicenter, randomized, controlled, double-masked pilot study was conducted in adults with dry eye diagnosis and at least one eye with corneal fluorescein staining ≥2 in at least one region or a sum of all regions ≥5 (National Eye Institute grading), basal Schirmer test score ≤10 mm, a cotton-swab stimulated Schirmer score ≥7 mm higher, and an Ocular Surface Disease Index score ≥23. Subjects were randomized to receive active intranasal neurostimulation or sham control intranasal stimulation 4 to 8 times per day. Assessments were scheduled before (unstimulated) and during (stimulated) device application at days 0, 7, 14, 30, and 90. The primary effectiveness endpoint was stimulation-induced change in Schirmer test (with anesthesia) score. Primary safety measure was incidence of device-related adverse events (AEs). Results: Fifty-eight subjects were randomized at nine sites in Australia and New Zealand; 56 completed the 90-day study. Stimulation-induced change in Schirmer score was significantly greater with active intranasal (mean ± SEM, 9.0 ± 2.0) than sham control intranasal stimulation (0.4 ± 0.6; P < 0.001) at day 90. Similar results were observed at days 0, 7, 14, and 30 (P < 0.001). No serious device-related AEs were observed. Mild nosebleed, the most common device-related AE, was reported in five (16.7%) subjects. Conclusions: Intranasal neurostimulation was effective in inducing acute tear production after 90 days of use and generally was well tolerated in subjects with dry eye disease.

"Off-the-Shelf" K2-EDTA for Calcific Band Keratopathy.

PURPOSE: To explore the effectiveness of "off-the-shelf" dipotassium-ethylenediaminetetraacetic acid (K2-EDTA) as an alternative to sodium EDTA as chelation therapy in removal of calcific band keratopathy (CBK). METHODS: This study was a retrospective case series involving 4 patients with CBK who underwent superficial keratectomy and subsequent chelation therapy with K2-EDTA in a single center (Coastal Eye Clinic) by the same surgeon. Visual acuity and symptomatic relief were the main outcomes measured in our study. RESULTS: All 4 participants in this study were female with an average age of 80.3 years. Three of the patients with reasonable baseline visual acuity experienced improved visual acuity at 1 month. The other patient with multiple ocular comorbidities and severely reduced visual potential reported symptomatic pain relief at 1-month follow-up after the intervention. CONCLUSIONS: K2-EDTA seems to be an effective alternative to disodium EDTA in its ability to clear calcific plaques and restore visual function. Because of the logistical difficulties associated with acquiring disodium EDTA, and the relative abundance of K2-EDTA in health-care facilities, we believe that our findings warrant further investigation into its use as a more accessible and cost-effective chelating agent in CBK.

Autoconjunctival Graft Compromise After Pterygium Surgery in a Patient Receiving Intravitreal Anti-Vascular Endothelial Growth Factor Injections.

PURPOSE: To report on a case of autoconjunctival graft compromise after pterygium surgery in a patient on long-term anti-vascular endothelial growth factor (anti-VEGF) therapy, due to the deleterious effects of anti-VEGF agents on ocular wound healing. METHODS: A white female in her early eighties presented with large right nasal pterygium, first noted 5 years previously. She also had macular degeneration and had been receiving monthly injections of ranibizumab, which was later switched to aflibercept. She proceeded to have a right nasal pterygium excision with a conjunctival autograft, 9 days after her last dose of intravitreal aflibercept. RESULTS: Surgery was uneventful; however, at the week 2 postoperative review, there was conjunctival graft dehiscence with melting of the graft and underlying sclera. The patient was administered hyperbaric oxygen treatments, topical antibiotics, steroids, and lubricating eye drops, and aflibercept injections ceased. The scleral melt slowly resolved and her aflibercept was restarted 3 months later. CONCLUSIONS: This case highlights the potential hazards of performing elective surgery in patients on VEGF inhibitors and the need for an appropriate interval between cessation/subsequent restart of anti-VEGF agents and surgery to be established.

Use of adjuvant hyperbaric oxygen therapy to support limbal conjunctival graft in the management of recurrent pterygium.

PURPOSE: To assess the role of hyperbaric oxygen therapy (HBOT) in the management of recurrent pterygium. METHODS: Thirty-nine eyes with recurrent pterygium were treated with surgical excision and limbal conjunctival autograft, followed by a course of HBOT. Patients were followed for development of recurrence. RESULTS: Of the 39 eyes, 18 had a known history of exposure to beta radiation or mitomycin C. The mean duration of follow-up in this group was 23.1 months. A single recurrence was noted in this group. For the remaining 21 eyes, the mean duration of follow-up was 19.4 months. No recurrences were recorded in this group. No significant complications from HBOT were recorded. CONCLUSIONS: The use of HBOT together with excision and limbal conjunctival autograft for recurrent pterygium is associated with a low recurrence rate. Adjuvant HBOT should be considered in the surgical management of recurrent pterygium.

Stimulation of the retina with a multielectrode extraocular visual prosthesis.

BACKGROUND: An extraocular approach to developing a retinal prosthesis for blind patients using electrodes placed on the outer surface of the eye is suggested. Experiments were carried out to determine the feasibility of this approach, and evaluate electrode configurations and parameters for stimulation. METHODS: In anaesthetized cats, a 21-electrode extraocular retinal prosthesis (ERP) array was sutured to the sclera over the lateral surface of the eye. Electrically evoked potentials (EEP) were recorded at the visual cortex bilaterally in response to retinal stimulation with the electrode array. Bipolar stimulation of the ERP array electrodes in horizontal and vertical configurations and at different interelectrode separations was investigated with biphasic constant-current pulses. RESULTS: Electrical stimulation of the lateral retina with an ERP elicited EEP that were higher in the ipsilateral visual cortex. The threshold for bipolar retinal stimulation was 500 microA. EEP amplitude increased with increases in stimulus pulse duration and current intensity. Retinal stimulation was slightly more effective with electrodes in a vertical as opposed to horizontal orientation. A larger interelectrode separation resulted in a higher EEP amplitude. CONCLUSIONS: Retinal stimulation with a prototype ERP array is demonstrated. The thresholds for retinal excitation are below safe charge-density limits for chronic neural stimulation. Ipsilateral localization of the EEP suggests that localized retinal stimulation is occurring. An ERP is a new approach to retinal prosthesis research, and might lead to the development of a low-resolution visual prosthesis for blind patients.

Evaluation of extraocular electrodes for a retinal prosthesis using evoked potentials in cat visual cortex.

OBJECTIVE: To assess the efficacy of a device using extraocular electrodes as a retinal prosthesis by evaluating the responses evoked in the visual cortex to electrical stimulation. METHODS: In anaesthetised cats, a lateral orbital dissection and ipsilateral parietal craniotomy was performed. Two extraocular retinal prosthesis (ERP) disc electrodes were sutured to the sclera on the lateral and superior aspects of the globe. Retinal stimulation was performed with charge-balanced constant-current pulses. Potentials evoked in the visual cortex were measured with a ball electrode placed on the lateral gyrus after removal of the dura. RESULTS: Stable attachment of the ERP electrodes to the globe was achieved with scleral sutures. Visual cortex responses were recorded with the electrodes in bipolar and monopolar configurations. The evoked response consisted of an early component with a peak around 8 ms, and a late component with a peak after 50 ms. Thresholds for evoking a response occurred at current intensities as low as 500 microA. Through extrapolation from evoked response amplitude data, thresholds as low as 300 microA were calculated. Cathodal monopolar stimulation demonstrated lower thresholds than anodal stimulation for evoking cortical responses. CONCLUSIONS: The ERP electrodes can be easily attached to the globe and are effective in electrically stimulating the retina, evoking responses in the primary visual cortex. Threshold charge-density was within safe limits for neural stimulation.

Feasibility of extraocular stimulation for a retinal prosthesis.

BACKGROUND: We present a new approach to developing a retinal prosthesis for blind patients based on extraocular stimulation of the eye with disc electrodes. METHODS: Experiments to assess the feasibility of using extraocular stimulation in a retinal prosthesis were carried out in anaesthetised adult cats (n=6). A craniotomy and lateral orbital dissection were performed. Ball or disc electrodes were placed on the posterior scleral surface of the eye after incision of the periorbita. Cortical potentials evoked by electrical stimulation with these electrodes were recorded at the primary visual cortex. The viability of adapting the Nucleus 24 auditory brainstem implant (ABI) as an extraocular retinal prosthesis was also investigated. RESULTS: Electrodes placed on the exterior of the eye could reliably evoke visual cortex responses for a variety of configurations. Threshold currents for eliciting an evoked response were lower than 100 microA with single pulses. Strength-duration curves and cortical activation maps were obtained for different stimulus paradigms. It was possible to excite the retina to evoke a cortical response using the electrodes and stimulus capabilities in a standard Nucleus 24 ABI. INTERPRETATION: It is possible to electrically stimulate the retina with electrodes placed in an extraocular location. Threshold currents required to elicit a response were low, and comparable to epiretinal implants. Prototype electrodes, and a potential implant, were found to be effective at retinal stimulation.