Cannabinoid applications in glaucoma

IntroductionGlaucoma is a slowly progressive optic neuropathy that is one of the leading causes of legal blindness throughout the world. Currently there is a limited group of topical drugs for the medical treatment of glaucoma is currently limited, and research needs to be focused on new therapeutic horizons, such as the potential usefulness of the cannabinoid agonists for the treatment of glaucoma.AimTo review the current scientific literature related to the beneficial effects derived from the different ways of administration of cannabinoids indicated for the glaucomatous optic neuropathy.DevelopmentCannabinoid receptors have shown an intense expression in ocular tissues implicated in the regulation of the intraocular pressure, as well as inner layers of the retina. Through activation of CB1 and CB1 specific receptors and through other still unknown pathways, the cannabinoid agonists have shown both a clear hypotensive, as well as an experimentally proved neuroprotective effect on retinal ganglion cells.ConclusionsSome cannabinoid agonists (WIN 55212-2, anandamide) have demonstrated, in experimental studies, to act as «ideal drugs» in the management of glaucoma, as they have been shown to have good tolerability after topical application, efficiently reduce intraocular pressure, and behave as neuroprotectors on retinal ganglion cells.Further studies as regards the safety and clinical assays must be carried out in order to examine the effectiveness of these drugs for the treatment of glaucoma in our daily clinical practice.     

Clonidine provides an allergy-free alternative in glaucoma patients with proven allergy to apraclonidine

· Purpose: The aim of this study was to determine allergic responses to clonidine hydrochloride 0.25% in glaucoma patients with proven allergic reaction to apraclonidine 0.5%. · Methods: Fifteen consecutive glaucoma patients with allergic reaction to apraclonidine were prospectively challenged with clonidine hydrochloride 0.25% and evaluated for recurrence of allergic reactions and efficacy of treatment. Intraocular pressure (IOP), conjunctival hyperemia, blood pressure and resting pulse rate were determined at baseline and after 1, 3, 6 and 12 months. · Results: None of the patients developed ocular allergic reaction during 12 months on clonidine therapy. Blood pressure and pulse rate did not change significantly with clonidine treatment. Clonidine caused a significant reduction of IOP from baseline. In one patient, topical clonidine caused fatigue, dizziness and dry mouth. · Conclusion: Clonidine did not cause allergic reaction in patients with proven allergy to apraclonidine, indicating that there is no cross-reactivity with apraclonidine. Due to the small series, however, we cannot assume that allergy will not occur with clonidine 0.25% given time and a larger number of patients. Received: 21 January 1999 Revised: 28 June 1999 Accepted: 29 July 1999     

ISRCTN12125882 - Influence of topical anti-VEGF (Ranibizumab) on the outcome of filtration surgery for glaucoma - Study Protocol

Background  

Excessive wound healing, with scarring of the episcleral tissue or encapsulation of the filtering bleb is the main reason for failure in trabeculectomy. Ranibizumab, an inhibitor of the Vascular Endothelial Growth Factor (VEGF), is seen as a promising candidate to prevent or treat extensive wound healing. We describe the design of a two phased study, i) assessing the local tolerability and safety of topical ranibizumab and ii) assessing the efficacy of topical ranibizumab against placebo in patients who underwent trabeculectomy with mitomycin C combined with phacoemulsification and intra ocular lens (IOL) implantation.     

Efficacy and tolerability of nortriptyline in the management of neuropathic corneal pain

PurposeNeuropathic corneal pain (NCP) is a recently acknowledged disease entity. However, there is no consensus in potential treatment strategies, particularly in patients with a centralized component of pain. This study aims to assess the efficacy and tolerability of the tricyclic antidepressant, nortriptyline, among NCP patients.MethodsPatients with clinically diagnosed NCP and a centralized component of pain, treated with oral nortriptyline, who had recorded pain scores as assessed by the ocular pain assessment survey at the first and last visit were included. Patients were excluded if they had any other ocular pathology that might result in pain or had less than 4 weeks of nortriptyline use. Demographics, time between visits, concomitant medications, systemic and ocular co-morbidities, duration of NCP, side effects, ocular pain scores, and quality of life (QoL) assessment were recorded.ResultsThirty patients with a mean age of 53.1 ± 18.5 were included. Male to female ratio was 8:22. Mean ocular pain in the past 24 h improved from 5.7 ± 2.1 to 3.6 ± 2.1 after 10.5 ± 9.1 months (p < 0.0001). Twelve patients (40.0%) had equal to or more than 50% improvement, 6 patients (20.0%) had 30–49% improvement, 6 patients (20.0%) had 1–29% improvement, 4 patients (13.3%) did not improve, while 2 patients (6.7%) reported increase in pain levels. Mean QoL improved from 6.0 ± 2.5 to 4.3 ± 2.4 (p = 0.019). Eight patients (26.6%) discontinued treatment due to persistent side effects, despite improvement by 22.4%.ConclusionNortriptyline was effective in relieving NCP symptoms in patients with centralized component and insufficient response to other systemic and topical therapies who tolerated the drug for at least 4 weeks. Nortriptyline may be used in the management of patients with NCP.     

Randomized masked trial of the clinical efficacy of MGO Manuka Honey microemulsion eye cream for the treatment of blepharitis

PurposeTo assess the clinical efficacy of a novel MGO Manuka Honey microemulsion (MHME) eye cream for the management of blepharitis.MethodsFifty-three participants (32 females, 21 males; mean ± SD age, 60 ± 12 years) with clinical signs of blepharitis were enrolled in a prospective, investigator-masked, randomized, paired-eye trial. The MHME eye cream (Manuka Health New Zealand) was applied to the closed eyelids of one eye (randomized) overnight for 3 months. Visual acuity, ocular surface characteristics, symptoms and tear film parameters were assessed at baseline, day 30, and day 90. Eyelid swab microbiology cultures were evaluated at baseline and day 90.ResultsBaseline measurements did not differ between treated and control eyes (all p > 0.05). Significant reductions in SANDE and SPEED symptomology scores were detected in treated eyes on days 30 and 90 (all p < 0.05), while clinical improvements in non-invasive tear film breakup time, lipid layer thickness, and inferior lid wiper epitheliopathy were observed on day 90 (all p < 0.05). Following the 3-month treatment period, ocular Demodex, Corynebacterium macginleyi, Propionibacterium acnes, and Staphylococcus epidermidis load decreased significantly in treated eyes (all p ≤ 0.001). There were no changes in visual acuity during the 90-day period (all p > 0.05), and no major adverse events were reported.ConclusionTopical overnight application of the MHME eye cream effected significant improvements in ocular surface symptomology, tear film stability and lipid layer thickness, and reduced lid margin staining, ocular Demodex and bacterial load. The favourable clinical efficacy and tolerability profile suggests promise for the MHME eye cream as a treatment for blepharitis management.Trial registration numberACTRN12616000539437.     

Treatment of ocular rosacea:comparative study of topical cyclosporine and oral doxycycline

AIM:To compare the effectiveness of topical cyclosporine A emulsion with that of oral doxycycline for rosacea associated ocular changes and dry eye complaints.METHODS:One hundred and ten patients with rosacea were screened. Thirty-eight patients having rosacea associated eyelid and ocular surface changes and dry eye complaints were included in the study. Patients were randomly divided into two groups:nineteen patients were given topical cyclosporine twice daily and nineteen patients were given oral doxycycline 100 mg twice daily for the first month and once daily for the following two months. Symptom and sign scores, ocular surface disease index questionnarie and tear function tests were evaluated at baseline and monthly for 3mo. Three months after results were compared with that of baseline.RESULTS:Mean values of symptom, eyelid sign and corneal/conjunctival sign scores of each treatment group at baseline and 3mo after treatments were compared and both drugs were found to be effective on rosacea associated ocular changes (P<0.001). Cyclosporine was more effective in symptomatic relief and in the treatment of eyelid signs (P=0.01). There was statistically significant increase in the mean Schirmer score with anesthesia and tear break up time scores in the cyclosporine treatment group compared to the doxycycline treatment group (P<0.05).CONCLUSION:Cyclosporine as a topical drug can be used in the treatment of rosacea associated ocular complications because it is more effective than doxycycline. In addition ocular rosacea as a chronic disease requires long term treatment and doxycycline has various side effects limiting its long term usage.     

Long-term brimonidine therapy in glaucoma patients with apraclonidine allergy

PURPOSE: To report the use of brimonidine in patients with a documented ocular allergy to apraclonidine. METHODS: We conducted a prospective, open-label study on the use of long-term brimonidine therapy in 57 patients with chronic glaucoma with documented allergy to apraclonidine. The study patients were placed on brimonidine tartrate 0.2%, 1 drop three times daily in one or both eyes, either as additive therapy to a medical regimen devoid of apraclonidine for further lowering of intraocular pressure (25 patients) or as a replacement for apraclonidine at the time of diagnosis of apraclonidine ocular allergy for maintenance of intraocular pressure control (32 patients). Clinical symptoms and signs of ocular allergy to brimonidine were monitored for up to 18 months. RESULTS: During the treatment period of up to 18 months, six (10.5%) of 57 patients developed slit-lamp biomicroscopic findings and subjective symptoms of an ocular allergic reaction that led to discontinuation of brimonidine treatment. All six patients developed ocular allergy to topical brimonidine 0.2% during the first 4 months of therapy. The addition of brimonidine 0.2% topical medication or the replacement of apraclonidine with brimonidine resulted in a significant decrease in mean intraocular pressure from 20.5+/-5.3 to 16.5+/-4.2 mm Hg (P < .0001) at the mean treatment period of 10.6+/-4.6 months (range, 0.5 to 18.0 months in all 57 patients: 5 to 18 months in the 51 patients without brimonidine allergy and 0.5 to 3.8 months in the six patients who developed brimonidine allergy. CONCLUSIONS: The incidence of ocular allergy after the use of brimonidine 0.2% topical medication for up to 18 months was 10.5% in patients with a documented history of apraclonidine allergy. Therefore, it is generally safe as well as efficacious to administer brimonidine to patients with an ocular allergy to apraclonidine.     

Combinatorial therapy with immunosuppressive,immunomodulatory and tear substitute eyedrops (“Triple Play”) in Recalcitrant Immunological Ocular Surface Diseases

PurposeThe current paradigm for therapy of recalcitrant ocular surface diseases (OSD) consists of a sequential, step-up treatment approach. A combinatorial topical therapy (anti-inflammatory/immunosuppressive [steroid] with immunomodulatory [pooled human immune globulin] and tear substitute [serum]) that simultaneously targets several immunological pathways may be more efficacious. This report evaluates if the combinatorial therapy resulted in clinical benefit in patients with recalcitrant OSD.MethodsWe performed a retrospective case study of patients receiving topical, preservative-free, compounded formulations of steroids, pooled human immune globulin, and serum tears. Outcome measures included visual acuity, ocular surface disease index (OSDI), ocular discomfort score, subjective global assessment (SGA), corneal staining, conjunctival redness, and slit lamp photographs.ResultsPatients consisted of one male and 11 females ranging in age from 27 to 87 years old. Pathologies included ocular graft-versus-host disease (n = 4), Sjögren's syndrome (n = 3), ocular cicatricial pemphigoid (n = 1), pemphigus vulgaris (n = 1), peripheral ulcerative keratitis (n = 1), Stevens-Johnson syndrome (n = 1), and giant papillary conjunctivitis (n = 1). All patients were “improved” or “much improved” on SGA after combinatorial therapy. There was a clinically meaningful reduction in OSDI, ocular discomfort, corneal staining, and conjunctival injection. Additionally, three patients had improvement in their visual acuity (one from 20/400 to 20/20). Adverse effects included increased intraocular pressure in two patients, presumably due to topical steroid use.ConclusionsCombinatorial therapy provides clinical benefit by reducing the symptoms and signs in recalcitrant OSD. Our study provides the rationale for performing prospective clinical trials to evaluate the efficacy of combinatorial therapy for treating recalcitrant OSD.     

Pathological consequences of anti-citrullinated protein antibodies in tear fluid and therapeutic potential of pooled human immune globulin-eye drops in dry eye disease

PurposeTo investigate the role of Anti-Citrullinated Protein autoantibodies (ACPAs) in the pathology of dry eye disease (DED) and the therapeutic potential of pooled human immune globulin-eye drops in these patients.MethodsWe investigated the presence of citrullinated proteins and ACPAs in ocular surface wash (OSW) and conjunctival impressions from patients with DED and determined the pathological consequences of OSW with high ACPA using in vitro experiments and in vivo murine models. We performed a randomized, double-masked, pilot clinical trial to determine the safety, tolerability and preliminary efficacy of using pooled human immune globulin-eye drops to treat DED patients with ACPAs in OSW.ResultsWe found that neutrophils are a source of citrullinated proteins on the ocular surface of DED patients. We detected significantly higher immunoglobulin amount and presence of several species of ACPAs in OSW from DED patients. We also found that OSW with high ACPA contributes to production of NETs, and that ACPAs cause ocular surface disease in murine eyes, both of which are reduced with addition of Immune globulins. As compared to Vehicle treatment, pooled human immune globulin-eye drops (IVIG 4 mg/mL) twice a day for 8 weeks caused significant reduction in signs and symptoms of DED with no difference in tolerability or adverse events.ConclusionsThis is the first report demonstrating ACPAs in OSW of DED patients and their contribution to ocular surface disease. The first-in-human clinical trial suggests that pooled immune globulin-eye drops are a potential new class of biologic therapies for Dry Eye patients.     

Clinicopathologic analysis of conjunctivochalasis and paste-pinch-cut conjunctivoplasty for management

ObjectiveTo correlate the histopathologic results of conjunctival specimens with clinical findings in patients with conjunctivochalasis and report the results of the paste-pinch-cut technique for management.Design: Retrospective chart review.SettingSingle tertiary ophthalmological centre (Ocular Surface Diseases and Dry Eye Clinic, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Md.).MethodsTwenty-five patients (32 eyes) with clinically significant conjunctivochalasis. All patients were referred for clinically significant dry eye without previous diagnosis of chalasis. Sixteen patients had an underlying inflammatory systemic condition. Intervention or Observation Procedure(s): Patients underwent surgery with paste-pinch-cut technique. Subjective dry eye symptoms and ocular surface staining scores (corneal and conjunctival staining using fluorescein and lissamine green respectively) were assessed at every visit.Main Outcome MeasuresChange in patient symptoms and ocular surface staining scores and histopathologic findings in conjunctival specimens.ResultsAfter surgery, significant improvement was achieved in dry-eye symptoms as well as both corneal and conjunctival staining scores in 29 eyes on reduced topical therapy. Only 3 eyes had persisting conjunctival lissamine staining. Light microscopic examination disclosed mild to moderate lymphoplasmocytic inflammation of the conjunctivae with areas of epithelial goblet cell loss, squamous metaplasia, stromal edema, and fibrosis.ConclusionConjunctivochalasis appears to be associated with significant inflammation in the setting of dry eye and underlying inflammatory systemic conditions. Although topical anti-inflammatory treatment could be attempted in the initial management, surgical excision should be considered in the absence of clinical response.     

Topical lambda-cyhalothrin in reducing eye oscillations in a canine model of infantile nystagmus syndrome

Purpose:To determine the ocular and systemic safety of using topical Lambda-Cyhalothrin (LCL) in a canine model of infantile nystagmus syndrome (INS). The rationale for this proposal is based on a case study of a patient whose INS improved after inadvertent ocular exposure to a pyrethroid pesticide containing LCL.Methods:After in-vitro safety testing and IUCAC approval, we studied increasing concentrations of topical LCL drops (0.002% to 0.07%) in canines with a purposely bred defect in the RPE65 gene resulting in both retinal degeneration and INS. We collected data on ocular and systemic effects and performed eye-movement recordings (EMR).Results:At the 0.07% concentration dose of LCL, there was minimal, reversible, conjunctival hyperemia. There was no other ocular or systemic toxicity. At the 0.06% dose, there was a visible decrease in the INS and EMR showed a 153%–240% increase in the nystagmus acuity function and a 30%–70% decrease in amplitude across gaze. There was also a 40%–60% decrease in intraocular pressure while on the drop in both eyes.Conclusion:This animal study suggests this new pharmacological agent has potential for topical treatment of both INS and diseases with raised intraocular pressure. Further, this new treatment approach confirms the importance of extraocular muscle proprioception in ocular motor diseases and their treatment.     

Evaluation of use of essential fatty acids in topical ophthalmic preparations for dry eye

PurposeEssential fatty acids (EFAs) as dietary supplements are used in treating dry-eye for reducing inflammation at the ocular surface. Their topical application in eye drops to deliver fatty acid (FA) directly to the ocular surface requires thorough investigation. Being lipids in nature EFAs can interact with tear lipids and affect tear stability. This study aimed at investigating the biophysical interactions of EFAs with Meibomian lipids.MethodsRheology of mixtures of Human Meibomian lipids with EFAs (LA-linoleic acid, ALA-alpha-linolenic acid), OA (oleic acid), and GLA (gamma-linolenic acid) was studied using Langmuir trough technology on an artificial tear solution at the ocular surface temperature. Pressure-area profiles were used to determine compressibility and elasticity of the mixed films.ResultsLA enhanced spreading of Meibomian lipids and increased their compressibility and elasticity which can be beneficial for tear stability. ALA condensed Meibomian lipids film with less elasticity deemed unfavourable for tear stability. OA expanded Meibomian lipids but decreased elasticity at high compressions making films less stable. GLA had little or no favourable effect on tear stability. Higher concentrations of FAs made films less stable.ConclusionsEFAs or OA in topical ophthalmic preparations can affect spread and stability of the tear film lipid layer. Rheology of mixed films should be tested using Langmuir trough technology to determine suitable type and amount of a lipid additive for therapeutic eye drops. In topical applications, the omega-6 LA (not omega-3 FA) at low concentrations (20 mol%) can be beneficial for enhancing tear stability in dry eye patients.     

Therapeutic efficacy of topical blockade of substance P in experimental allergic red eye

PurposeAllergic conjunctivitis is the most common cause leading to ocular redness (OR). Herein, using an animal model of allergic OR, we evaluated the therapeutic efficacy of topical blockade of substance P (SP) in treating red eye.MethodsAllergic OR was induced in guinea pigs with topical histamine. Ocular SP was blocked using a specific SP receptor (neurokinin-1 receptor, NK1R) antagonist, L-703,606, via topical application 10 min before or 10 min after histamine instillation. Animal eyes were examined and a series of images were taken for up to 60 min post-OR induction. The severity of redness was analyzed using the quantitative ocular redness index (ORI). At the end of clinical examination, conjunctival tissues were collected for histological examination of conjunctival blood vessels and infiltrating eosinophils and neutrophils. In addition, SP concentration was quantified in the tear fluid and expression levels of inflammatory cytokines were assessed in the conjunctival tissues.ResultsTopical histamine application successfully induced red eye, evidenced by the significantly increased ORI during the observation period, with peak values at 10 min, along with significantly increased levels of SP in the tears. Topical treatment with L-703,606, either before histamine application or at the time of peak ORI, effectively reduced ORI and suppressed conjunctival blood vessel dilation, along with decreased eosinophil and neutrophil infiltration, and inflammatory cytokine expression in the conjunctiva, as well as reduced SP levels in the tears.ConclusionsTopical blockade of SP effectively prevents and treats allergy-related ocular redness by suppressing blood vessel dilation and allergic inflammation.     

Luz pulsada intensa combinada con expresión de las glándulas de Meibomio para el tratamiento del chalación

ObjectiveTo investigate the efficacy and safety of an intense pulsed light (IPL) combined IPL treatment protocol for meibomian gland dysfunction (MGD)/dry eye disease (DED) with IPL applied directly to the eyelids, associated with meibomian gland (MG) expression for the treatment of chalazion.Material and MethodsRetrospective case series study. Patients presenting with chalazion received a combined IPL therapy treatment consisting of using the usual IPL protocol for DGM/EOS using a fluence according to skin type according to Fitzpatrick, followed by a second phase (in the same session) of IPL application directly on the eyelids of both eyes using a fluence of 10 J/cm2. All patients then received GM expression, eyelid hygiene, topical antibiotic and topical ocular anti-inflammatory medication. Adverse effects related to this protocol were assessed at each IPL session.ResultsTwenty-six chalazions from nineteen patients (24 eyes) with a mean age of 49.89 ± 20.43 years were included. An average of 2.07 ± 0.97 IPL sessions were required for chalazion resolution. The combined treatment of IPL protocol and GM expression showed 96.15% efficacy and no adverse effects were observed.ConclusionsCombined IPL treatment for DGM/EOS with IPL applied directly on the eyelids and GM expression could be effective and safe for the treatment of chalazions.     

Intraocular pressure elevation from topical difluprednate use

IntroductionDifluprednate ophthalmic emulsion 0.05% (Durezol?, Alcon, Fort Worth, Texas) is a topical difluorinated derivative of prednisolone with potent anti-inflammatory activity. Difluprednate 0.05% has a reported associated increase in intraocular pressure (IOP) in 3% of patients. Although the occurrence may be low, the possible elevation in IOP may be substantially higher than commonly encountered with other topical steroids.Case ReportsA 49-year-old black man presented with a traumatic anterior uveitis recalcitrant to traditional prednisolone acetate 1% treatment. The patient was switched to difluprednate 0.05% in an attempt to better control the ocular inflammation. Although the patient did not exhibit an IOP response after 4 weeks of treatment with prednisolone acetate 1%, he did experience a pressure response within 2 weeks of initiating difluprednate treatment, resulting in an IOP increase from 9 mmHg to 48 mmHg with subsequent microcystic edema.A 44-year-old black woman presented with recurrent scleritis resistant to topical prednisolone acetate, loteprednol etabonate, and oral nonsteroidal anti-inflammatory therapy. Topical loteprednol 0.5% was replaced by difluprednate 0.05%. All evidence of ocular inflammation was eradicated with the changed therapy. IOP rose in the difluprednate-treated eye from 18 mmHg to 34 mmHg over the course of 18 days. In both cases, the IOP elevation was managed rapidly with the discontinuation of difluprednate and temporary use of IOP-reducing agents with no lasting adverse effects.ConclusionDifluprednate 0.05% is a new topical therapeutic option indicated for the treatment of inflammation and pain management associated with ocular surgery with an off-label potential for treatment of other anterior segment inflammatory conditions. However, clinicians need to be aware of the potential risk for significant and potentially rapid onset of IOP increase with this medication and manage patients accordingly.     

Meibomian gland dysfunction is suppressed via selective inhibition of immune responses by topical LFA-1/ICAM antagonism with lifitegrast in the allergic eye disease (AED) model

PurposeThe etiology of meibomian gland dysfunction (MGD) is incompletely understood, despite being a common ophthalmic condition and an area of unmet medical need. It is characterized by an insufficiency in glandular provision of specialized lipids (meibum) to the tear film and is a major cause of dry eye. Work in the allergic eye disease (AED) mouse model has revealed an immunopathogenic role in MGD causation, now raising interest in the applicability of immunomodulatory therapies. As such, we herein ask whether inhibition of lymphocyte function associated antigen (LFA)-1/intracellular adhesion molecules (ICAM)-1 signaling via topical lifitegrast administration has a therapeutic effect on MGD in AED mice.MethodsMice were induced with AED by i.p. injection of ovalbumin (OVA) mixed with alum and pertussis toxin, followed 2 weeks later by once daily topical OVA challenges for 7 days. Mice were treated topically with 5% lifitegrast ophthalmic solution or vehicle (PBS) 30 min prior to challenge. We developed a clinical ranking method to assess MGD severity, and also scored clinical allergy. Conjunctivae and draining lymph nodes were collected for flow cytometry.ResultsTopical lifitegrast significantly inhibited clinical MGD severity, which was associated with diminished pathogenic T_H17 cell and neutrophil numbers in the conjunctiva. No significant change in conjunctival T_H2 cells or eosinophils, and only marginal differences in ocular allergy were observed.ConclusionsIn AED mice, lifitegrast inhibited MGD severity marked by a reduction in select immune populations in the conjunctiva. Our findings warrant future examination of lifitegrast in the treatment of patients with forms of MGD.     

Intraocular pressure-lowering effects of commonly used fixed combination drugs with timolol in the management of primary open angle glaucoma

AIM:To evaluate intraocular pressure (IOP)-lowering effect and ocular tolerability of brimonidine/timolol, dorzolamide/timolol and latanoprost/timolol fixed combination therapies in the management of primary open angle glaucoma.METHODS:Each drug was administered for two months, after which a circadian tonometric curve was recorded using a Goldmann applanation tonometer. Ocular discomfort (conjunctival hyperemia, burning or stinging, foreign body sensation, itching, ocular pain) of each eye was assessed by the subject on a standardized ocular discomfort scale.RESULTS:Among the three study groups, there were no significant differences in the mean baseline IOP measurements, mean 2^nd mo IOP measurements, and mean (%) change of IOPs from baseline. Among the three study groups, there were no significant differences in the mean IOP measurements obtained at circadian tonometric curves at baseline and at two months controls. In sum brimonidine/timolol, dorzolamide/timolol and latanoprost/timolol fixed combination therapies showed similar effects on IOP levels.CONCLUSION:Brimonidine/timolol, dorzolamide/timolol and latanoprost/timolol fixed combination therapies showed similar lowering efficaties on IOP levels whereas there was no any difference between each other.     

Dupilumab-associated ocular surface disease: presentation,management and long-term sequelae

ObjectivesTo determine the presenting features of ocular surface disease in patients with atopic dermatitis (AD) treated with dupilumab at a tertiary, university hospital. To establish the need for treatment of dupilumab-associated ocular surface disease and report any long-term effects on the ocular surface.MethodsA retrospective analysis of consecutive patients treated with dupilumab for AD between January 2017 and August 2019 was undertaken. Data were collected on demographics, incidence and type of ocular disease features, natural history and treatment.ResultsA total of 50% (14/28) patients developed ocular symptoms with a mean time of onset of 6.75 (±6.1) weeks from starting dupilumab. Of these, 69% (9/13) were diagnosed with conjunctivitis associated with cicatrisation in two patients and periorbital skin changes in four. Of these nine, four had prior history of atopic keratoconjunctivitis. All were treated with topical steroids; two required additional ciclosporin drops. In all, 67% (6/9) patients went on to have on-going ocular inflammation requiring maintenance drops at a mean of 16 (±6.9) months of follow-up. All patients had improvement in their AD severity; only one patient discontinued dupilumab due to ocular side effects.ConclusionThe rate of dupilumab-associated ocular surface disease was 32%. Periorbital skin changes and conjunctival cicatrisation were noted in association with conjunctivitis. Ocular surface disease improved on topical steroids and ciclosporin but 67% of patients needed on-going treatment. Close liaison with an ophthalmologist should be considered in those patients who develop conjunctivitis or have a past history of severe ocular surface disease.Subject terms: Eye manifestations, Conjunctival diseases     

Topical application of cannabinoid-ligands ameliorates experimental dry-eye disease

PurposeDry eye disease (DED) is a multifactorial disease, with limitations regarding efficacy and tolerability of applied substances. Among several candidates, the endocannabinoid system with its receptors (CB1R and CB2R) were reported to modulate inflammation, wound healing and pain, which are also core DED pathomechanisms. This study is to investigate the therapeutic responses of Δ-9 tetrahydrocannabinol (a non-selective agonist) and two selective antagonists, SR141716A (CB1R antagonist) and SR144528 (CB2R antagonist), as a topical application using a DED mouse model.MethodExperimental DED was induced in naïve C57BL/6 mice. Expression of CBR at the ocular surface of naïve and DED mice was determined by qPCR and in-situ hybridization. Either THC or CBR antagonists were compounded in an aqueous solution and dosed during the induction of DED. Tear production, cornea sensitivity, and cornea fluorescence staining were tested. At the end of each experiment, corneas were stained with β3-tubulin for analysis of corneal nerve morphology. Conjunctiva was analyzed for CD4⁺ and CD8⁺ infiltration.ResultsCB1R and CB2R are present at the ocular surface, and desiccating stress increased CBR expressions (p < 0.05). After 10 days of DED induction, treated groups demonstrated a reduced CBR expression in the cornea, which was concurrent with improvements in the DED phenotype including fluorescence staining & inflammation. Applying THC protected corneal nerve morphology, thus maintained corneal sensitivity and reduced CD4⁺ T-cell infiltration. The CB1R antagonist maintained cornea sensitivity without changing nerve morphology.ConclusionsEndocannabinoid receptor modulation presents a potential multi-functional therapeutic approach for DED.