Chronic Conjunctival Chemosis-A New Ocular Side Effect of Crizotinib.

Crizotinib, a targeted molecular therapy drug which inhibits tyrosine kinase, is approved for treatment of non-small cell lung carcinoma which has some ocular side effects like photopsia and delayed dark adaptation.This report documents a unique case of persistent conjunctival chemosis likely due to side effects of crizotinib therapy. A 64-year-old gentleman on crizotinib for metastatic adenocarcinoma of the lung presented with conjunctival chemosis in right eye which appeared 1 month after uneventful clear corneal phacoemulsification surgery. The patient was on crizotinib 250 mg twice a day started 2 months before cataract surgery. Clinical examination revealed marked inferior bulbar conjunctival edema of the right eye. Anterior segment optical coherence tomography, slit-lamp photographs, and magnetic resonance imaging orbit and systemic investigation were done to rule out other causes of conjunctival edema. Magnetic resonance imaging shows conjunctival and preseptal edema around both eye and thinning of the optic nerve in the right eye. Anterior segment optical coherence tomography revealed elevated hyper-reflective thickened conjunctival layer with dilated empty thin wall dark spaces of varying caliber. Chemosis was persisted for the next 3 months and not responded to oral acetazolamide, topical steroid and decongestive eyedrops. After 3 months, crizotinib was discontinued by oncologist due to drug intolerance and surprisingly within 1 week, the conjunctival edema was disappeared totally. To the best of the authors' knowledge, this is the first reported case of persistent unilateral non-inflammatory conjunctival chemosis caused by crizotinib. The physicians should be vigilant about these complications.

Adverse reactions to 1% cyclopentolate eye drops in children: an analysis using logistic regression models.

PURPOSE: To determine the frequency, symptoms and risk factors for adverse reactions to two-times instillation of 1% cyclopentolate in children. STUDY DESIGN: Prospective, observational study. METHODS: The subjects were 646 patients who underwent cycloplegic refraction with cyclopentolate (mean age; 7.0 ± 3.5 years, age range; 0-15 years). Five minutes after instillation of 0.4% oxybuprocaine hydrochloride, a 1% cyclopentolate eye drop was instilled twice, with an interval of 10 min. Fifty minutes later, two certified orthoptists evaluated adverse reactions using a questionnaire and interviewed the patients' guardians. The relationship between the adverse reaction rates and age, gender, additional instillation, complications of the central nervous system (CNS), time of day and season were analysed using binominal and polytomous logistic regression models. RESULTS: The overall frequency of adverse reactions was 18.3% (118/646 patients). The main symptoms included conjunctival injection (10.5%, 68/646), drowsiness (6.8%, 44/646) and facial flush (2.2%, 14/646). The odds ratio (OR) of conjunctival injection increased with patient's age (p < 0.05), in boys (p < 0.01) and in winter (p < 0.001). In contrast, the OR of drowsiness decreased with age (p < 0.001). Facial flush was observed mostly in children younger than 4 years. CNS complications were not a significant risk factor for any of the symptoms. CONCLUSIONS: Adverse reactions to 1% cyclopentolate eye drops were more frequent than previously expected, but all were mild and transient. The probability of each symptom was associated with a clear age-specific trend.

Efficacy of eye drops containing crosslinked hyaluronic acid and CoQ10 in restoring ocular health exposed to chlorinated water.

PURPOSE: A prospective, open-label study in 20 professional swimmers evaluated the efficacy and safety of an ophthalmic solution containing crosslinked hyaluronic acid, coenzyme Q10, and vitamin E TPGS in releasing eye irritation and restoring ocular surface damages after prolonged exposure to chlorinated water. METHODS: Individually, one eye was instilled with the ophthalmic solution and the other used as a comparator. Eye drops were self-administered three times a day for 2 months. Tear film breakup time (primary endpoint), Schirmer I test, beating of eyelashes/min, tear osmolarity, corneal and conjunctival staining with fluorescein, Ocular Surface Disease Index questionnaire, subject satisfaction, visual acuity (secondary endpoints), and Efron Grading Scale were evaluated at screening/baseline (V1), week 1 (V2), week 2 (V3), week 4 (V4), and week 8 (V5). RESULTS: After 2 months, breakup time test significantly improved in the treated eyes (+1.67 s) compared to control (-3.00 s) (p = 0.0002). Corneal and conjunctival surfaces of treated eyes recovered significantly compared to control eyes when assessed by fluorescein staining (p < 0.0001), Ocular Surface Disease Index (p < 0.05), and visual analog scale (p = 0.0348) scores. Improvements were also observed with Schirmer I test, beating of eyelashes, and tear osmolarity, despite without statistical significance. Efron Grading Scale was consistent with the other tests. The ocular tolerability was excellent. CONCLUSION: The adequate combination of crosslinked hyaluronic acid, coenzyme Q10, and vitamin E TPGS, contained in the ophthalmic solution VisuXL®, has been shown to protect ocular surface from potential damages originating from prolonged exposure to chlorinated water. VisuXL may represent a compelling treatment in other situations beyond dry eye syndrome.

Ocular surface response and subjective symptoms associated to lens care solutions in Palestine.

PURPOSE: To compare the biocompatibility and subjective symptoms of four multipurpose solutions marketed in Palestine with hydrogel contact lenses. METHODS: 50 habitual soft contact lens wearers were recruited in this interventional crossover study. Subjects were asked to attend the optometry clinic five times. A new pair of hydrogel lenses (Bioxifilcon-B) were fitted each time. This pair was soaked randomly overnight in one of the following four-multipurpose solutions (NEOPLUS®, AvizorUnicaSensitive®, ReNuMultiPlus® and COMPLETERevitaLens®) which contain different disinfecting agents (PHMB, Phx, PAPB, and PQ-1+Alexidine, respectively), or non-preserved saline. At each visit, corneal staining, ocular redness and subjective symptoms were assessed. RESULTS: The percentage of corneal staining increased significantly (P≤0.050) after soaking the lenses with PHMB (86%), PAPB (64%) and Phx (32%) based-solutions. However, a non-significant increase was noticed after the use of PQ-1+Alexidine based solution (30%, P=0.083). Ocular redness evaluation showed a significant increase (P≤0.050) in limbal hyperemia after the use of all solutions, while bulbar redness was significantly increased after the use of biguanide-based solutions (P≤0.050). The subjective assessment analysis showed a non-significant change in comfort, dryness, photophobia and scratchiness (P≥0.050) at 2-h intervention using all solutions, except for the PHMB based solution which showed a significant change in subjective symptoms (P≤0.050). CONCLUSION: The combination of Bioxifilcon-B hydrogel contact lenses and solution containing PHMB, PAPB and Phx-disinfectants induced a significant increase in corneal staining after 2h of CL-wear with a higher severity when the PHMB-based solution was used, while the PQ-1+Alexidine-based solution did not. Only the PHMB-based solution triggered a significant change in subjective symptoms which might which suggests that it might be related to the severity of staining rather than the induction of staining.

Brimonidine-induced unilateral ocular lichen planus: a case report / Líquen plano ocular unilateral induzido por brimonidina: relato de caso

ABSTRACT This report was written to describe a case of unilateral brimonidine-induced conjunctival lichen planus. Because the ophthalmic examination indicated chronic conjunctivitis or drug-induced pseudopemphigoid, the patient underwent thorough ophthalmic and systemic examinations, as well as conjunctival biopsy and direct immunofluorescence studies. A 71-year-old woman with unilateral left eye findings of chronic conjunctivitis was referred to our Ophthalmology Department. The patient reported that chronic conjunctivitis began shortly after she initiated use of topical brimonidine. Ophthalmic examination revealed foreshortening of the inferior fornix and symblepharon. Conjunctival biopsy revealed submucous lymphocytes and shaggy distribution of fibrinogen on direct immunofluorescence; this was suggestive of ocular lichen planus. No other systemic lesions were found that were consistent with the presentation of lichen planus. A good response was observed to topical cyclosporine treatment. To our knowledge, this may be the first report of unilateral ocular lichen planus without systemic findings. The correlation with the initiation of topical brimonidine suggests that this might be the first case of biopsy-confirmed brimonidine-induced ocular lichen planus.

RESUMO Este relato é para descrever um caso de líquen plano conjuntival unilateral induzido por brimonidina. Como o exame oftalmológico indicava conjuntivite crônica ou pseudopenfigóide induzido por medicamento, o paciente foi submetido a exames oftalmológicos e sistémicos completos, além de biópsia conjuntival e estudos de imunofluorescência direta. Uma mulher de 71 anos de idade com achados unilaterais do olho esquerdo de conjuntivite crônica foi encaminhada ao nosso departamento de Oftalmologia. A paciente relatou que a conjuntivite crônica começou logo após o início do uso da brimonidina tópica. O exame oftalmológico revelou encurtamento do fórnice inferior e do symblepharon. A biópsia conjuntival revelou linfócitos submucosos e distribuição felpuda de fibrinogênio na imunofluorescência direta; isso era sugestivo de líquen plano ocular. Não foram encontradas outras lesões sistêmicas compatíveis com a apresentação do líquen plano. Uma boa resposta foi observada no tratamento tópico com ciclosporina. Pelo nosso conhecimento, este pode ser o primeiro relato de líquen plano ocular unilateral sem achados sistêmicos. A correlação com o início da brimonidina tópica sugere que este pode ser o primeiro caso de líquen plano ocular induzido por brimonidina confirmado por biópsia.

Ectopic Ocular Surface Calcification in Patients With Hypophosphatasia Treated With Asfotase Alfa.

PURPOSE: To assess for ectopic ocular calcification in a series of patients with hypophosphatasia (HPP) treated with asfotase alfa, a recombinant tissue-nonspecific alkaline phosphatase. METHODS: This is a retrospective analysis of subjects enrolled at Duke University Medical Center in ENB-009-10 (ClinicalTrials.gov: NCT01163149), a randomized controlled trial of asfotase alfa in adolescents and adults with HPP. Seven patients between the ages of 45 and 66 years diagnosed with HPP based on clinical features and low serum alkaline phosphatase levels were enrolled at our site. Subjects were randomized to receive either daily subcutaneous injections of asfotase alfa or no treatment. After 24 weeks, during the open-label extension phase, all subjects received treatment for at least 4 years. All subjects underwent comprehensive eye examinations at baseline and at 24-week intervals throughout the study to assess for development of ocular calcifications. RESULTS: By week 120, all 7 subjects developed asymptomatic white refractile deposits in the interpalpebral perilimbal conjunctiva. Biopsy of the conjunctival lesions in 2 subjects revealed elastosis with subepithelial calcification. The lesions were nonprogressive and in 5 subjects exhibited some degree of regression. CONCLUSIONS: Asfotase alfa was invariably associated with development of mild focal conjunctival calcification, likely through disinhibition of hydroxyapatite crystal propagation. The calcifications were not symptomatic or vision-threatening and should not preclude enzyme replacement therapy for patients with this rare and often debilitating disease.

Brimonidine-induced unilateral ocular lichen planus: a case report.

This report was written to describe a case of unilateral brimonidine-induced conjunctival lichen planus. Because the ophthalmic examination indicated chronic conjunctivitis or drug-induced pseudopemphigoid, the patient underwent thorough ophthalmic and systemic examinations, as well as conjunctival biopsy and direct immunofluorescence studies. A 71-year-old woman with unilateral left eye findings of chronic conjunctivitis was referred to our Ophthalmology Department. The patient reported that chronic conjunctivitis began shortly after she initiated use of topical brimonidine. Ophthalmic examination revealed foreshortening of the inferior fornix and symblepharon. Conjunctival biopsy revealed submucous lymphocytes and shaggy distribution of fibrinogen on direct immunofluorescence; this was suggestive of ocular lichen planus. No other systemic lesions were found that were consistent with the presentation of lichen planus. A good response was observed to topical cyclosporine treatment. To our knowledge, this may be the first report of unilateral ocular lichen planus without systemic findings. The correlation with the initiation of topical brimonidine suggests that this might be the first case of biopsy-confirmed brimonidine-induced ocular lichen planus.

Evaluation of offset of conjunctival hyperemia induced by a Rho-kinase inhibitor; 0.4% Ripasudil ophthalmic solution clinical trial.

Glaucoma leads to irreversible blindness. Numerous anti-glaucoma eye drops have been developed. Unfortunately, many patients with glaucoma still suffer from progressive visual disorders. Recently, ripasudil hydrochloride hydrate, a selective Rho-associated protein kinase inhibitor, was launched for the treatment of glaucoma. However, adverse events, such as conjunctival hyperemia, are often noted in clinical trials using healthy subjects. Therefore, we investigated the onset, offset, and kinetic changes of conjunctival hyperemia induced by ripasudil ophthalmic solution in patients with open-angle glaucoma or ocular hypertension who had already been treated with anti-glaucoma eye drops other than ripasudil. Conjunctival hyperemia was evaluated by both clinical grading by 3 ophthalmic physicians and pixel coverage of conjunctival blood vessels determined by conjunctival hyperemia-analyzing software. Conjunctival hyperemia appeared within 10 min post-instillation in most of the participants. Clinical grade and pixel coverage increased significantly 10 min post-instillation and then decreased. In most of the participants, hyperemia resolved within 2 h. Median conjunctival hyperemia offset was 90 min. A tendency of monotonic increase was observed between clinical grade and pixel coverage. Taken altogether, hyperemia induced by ripasudil was transient in glaucoma patients who had already been treated with anti-glaucoma eye drops other than ripasudil.

Objective ocular surface tolerance in patients with glaucoma treated with topical preserved or unpreserved prostaglandin analogues.

PURPOSE: Preservatives in glaucoma medications have been associated with ocular toxicity. We compared ocular signs and symptoms in patients with open-angle glaucoma or ocular hypertension treated in monotherapy with preserved or preservative-free prostaglandin analogues. METHODS: Observational cross-sectional clinical study in real life. 82 patients treated for at least 6 months with prostaglandin analogue were assessed for intraocular pressure, ocular symptoms and ocular signs including conjunctival hyperaemia, tear break-up time and tear meniscus height measured using objective and non-invasive methods (OCULUS Keratograph 5M). Patients presenting with symptoms of ocular toxicity with preserved prostaglandin analogues were switched to preservative-free latanoprost, and a second assessment was processed 6 months after. RESULTS: At inclusion, 30 (36.6%) patients were treated with preservative-free latanoprost, 25 (30.5%) with preserved latanoprost, 16 (19.5%) with preserved travoprost and 11 (13.4%) with preserved bimatoprost. Patients treated with preservative-free latanoprost reported significantly less ocular symptoms upon instillation (mainly burning) and between instillations than patients treated with preserved prostaglandin analogues. The mean conjunctival hyperaemia (limbal + bulbar) was significantly lower with preservative-free latanoprost (2.08 ± 0.55) compared to preserved latanoprost (2.50 ± 0.7, p = 0.0085), preserved travoprost (2.67 ± 0.82, p = 0.0083) and preserved bimatoprost (2.68 ± 0.67, p = 0.0041). There were no relevant between-group differences in mean tear meniscus height and break-up time. Ocular symptoms and conjunctival hyperaemia improved when preserved prostaglandin analogues were switched to preservative-free latanoprost for 6 months while intraocular pressure reduction was maintained. CONCLUSION: Overall, this study suggests a better subjective and objective ocular tolerance when patients were treated with preservative-free latanoprost than with other preserved prostaglandin analogues monotherapy. Switching to preservative-free latanoprost maintained intraocular pressure at the same level as preservative prostaglandin analogue, but improved ocular surface tolerance.

"Eye Dropping"-A Case Report of Transconjunctival Lysergic Acid Diethylamide Drug Abuse.

PURPOSE: To report a case of bilateral toxic corneal and conjunctival epitheliopathy secondary to administration of filter paper impregnated with lysergic acid diethylamide (LSD) in the inferior conjunctival fornices. METHODS: This is a single case report of an 18-year-old man who presented to the emergency department with acute, bilateral eye pain and redness of 24 hours. The patient admitted to placing folded strips of blotting paper impregnated with LSD into the inferior fornices of his eyes the previous night. RESULTS: The patient was found to have localized bilateral corneal and conjunctival abrasions with underlying subconjunctival hemorrhage. Conjunctival abrasion was "kissing," involving the bulbar and palpebral conjunctiva, corresponding to the presumed location of the filter paper. There was no corneal stromal opacification. He was lost to follow up within 1 week of initial presentation but stated that his symptoms improved. CONCLUSIONS: To the best of our knowledge, this is the first reported case of bilateral hemorrhagic conjunctival abrasion and corneal abrasion secondary to LSD. "Kissing" conjunctival lesions, which have been previously reported with heroin use, should raise suspicion for drug abuse.

Association between oral fluoroquinolone use and lateral canthal tendon rupture: case report.

It is well established and documented that fluoroquinolone use is associated with the development of tendinopathy. However, little is known about the possible effects of this class of antibiotics on the orbit. We present a case of lateral canthal tendon rupture that presented with an acute right lower eyelid ectropion in a young, renal compromised patient in the setting of recent fluoroquinolone use for pneumonia. Eye care clinicians need to be aware of the possible effects of fluoroquinolones on the eyelids.

Hydrogen-peroxide and silicone-hydrogel contact lenses: Worsening of external eye condition and tear film instability.

PURPOSE: The aim is discussing the origins of worsening of external eye condition (EEC) and of tear film (TF) instability after wear of silicone-hydrogel contact lenses (CLs) with hydrogen-peroxide (H2O2) care system. METHODS: EEC and TF stability were evaluated before and after 15days of wear combined with different care systems: (1) H2O2, (2) detergent solution and H2O2, (3) multipurpose solution (MPS), (4) H2O2 and artificial tears. In-vitro cell mortality tests were performed after 24h cell incubation with CLs treated with H2O2. Photon correlation spectroscopy (PCS) was carried out on tears of non-wearers and CL wearers who used MPS or H2O2 solution. RESULTS: Worsening of EEC was observed only for the group using H2O2 (group 1). In-vitro, cell mortality was found higher for worn CL than for unworn CLs. Worsening of TF stability was observed regardless of care system and also PCS results on tears of CL wearers were found different compared to non-wearers regardless of care system. The only observed remedy for tear instability of CL wearers was found to be the administration of artificial tears. CONCLUSIONS: Worsening of EEC of CL wearers using H2O2 is attributed to H2O2 scarce cleaning efficacy, which can be solved by adding a CL detergent solution. The origin of TF instability is found to be different. A remedy was found to be the administration of artificial tears, whose effect could be attributed either to the role of specific components or to rinsing and replacement of TF during wear.

Use of Topical Cannabinomimetic Palmitoylethanolamide in Ocular Surface Disease Associated with Antiglaucoma Medications.

PURPOSE: Chronic use of topical hypotensive therapies in glaucoma patients leads to chronic inflammation of the ocular surface, which decreases the success rate of long-term glaucoma management. The aim of this study is to evaluate the effect of topical palmitoylethanolamide (PEA) (Defluxa©), a well-known anti-inflammatory and analgesic agent, in suppressing the ocular surface inflammation associated with the use of hypotensive eye drops. METHODS: In a pilot clinical trial, we enrolled 15 glaucomatous patients who received topical PEA (Defluxa) in addition to the current antiglaucoma drugs, while 15 glaucomatous patients did not receive any additional treatment. At 3 different time points (day 0, 15, and 30), signs of ocular surface involvement, adverse events, visual acuity, and intraocular pressure were assessed. RESULTS: Topical PEA (Defluxa) was effective in increasing the Schirmer test (P < 0.05) and the tear film breakup time (T-BUT) (P < 0.0001), and improving the conjunctival hyperemia (P < 0.0001) by day 30, compared to baseline. Compared to control, by day 15, the conjunctival hyperemia score was significantly decreased in the PEA (Defluxa) group (P < 0.01), while the T-BUT and the Schirmer Test achieved a significant improvement by day 30 (P < 0.05; P < 0.01). DISCUSSION: Our data suggests that topical PEA (Defluxa) is a safe, effective, and generally well-tolerated treatment to prevent or suppress ocular surface inflammation attributable to chronic glaucoma treatment.