Is there a rational basis for cannabinoids research and development in ocular pain therapy? A systematic review of preclinical evidence.

BACKGROUND: Purpose of the present systematic review is to investigate preclinical evidence in favor of the working hypothesis of efficacy of cannabinoids in ocular pain treatment. METHODS: Literature search includes the most relevant repositories for medical scientific literature from inception until November, 24 2021. Data collection and selection of retrieved records adhere to PRISMA criteria. RESULTS: In agreement with a priori established protocol the search retrieved 2471 records leaving 479 results after duplicates removal. Eleven records result from title and abstract screening to meet the inclusion criteria; only 4 results are eligible for inclusion in the qualitative synthesis impeding meta-analysis. The qualitative analysis highlights the antinociceptive and anti-inflammatory efficacy of Δ8-tetrahydrocannabinol, cannabidiol and its derivative HU-308 and of new racemic CB1 allosteric ligand GAT211 and its enantiomers GAT228 and GAT229. Moreover, CB2R agonists RO6871304 and RO6871085 and CB2R ligand HU910 provide evidence of anti-inflammatory efficacy. CB2 agonist HU308 reduces of 241% uveitis-induced leukocyte adhesion and changes lipidome profile. Methodological and design issues raise concern of risk of bias and the amount of studies is too small for generalization. Furthermore, the ocular pain model used can resemble only inflammatory but not neuropathic pain. CONCLUSIONS: The role of the endocannabinoid system in ocular pain is underinvestigated, since only two studies assessing the effects of cannabinoid receptors modulators on pain behavior and other two on pain-related inflammatory processes are found. Preclinical studies investigating the efficacy of cannabinoids in ocular inflammatory and neuropathic pain models are needed to pave the way for clinical translation.

Dupilumab-Associated Ocular Surface Disease: Clinical Characteristics, Treatment, and Follow-Up.

PURPOSE: A consecutive case series of patients with dupilumab-associated ocular surface disease (DAOSD) that describes common ocular symptoms and signs, proposes a symptom disease severity grading system, and describes treatment strategies of DAOSD patients was evaluated. METHODS: A retrospective chart review of patients with concomitant dupilumab-treated atopic dermatitis and DAOSD with ophthalmic evaluation between January 2014 and May 2019 was conducted. RESULTS: Twenty-nine patients (mean age 46 years, M/F: 12/17) with 57 ophthalmic exams were identified. The most common ocular symptoms included irritation/pain (n = 28, 97%), redness (n = 24, 83%), pruritus (n = 18, 62%), discharge (n = 18, 62%), and light sensitivity (n = 6, 21%). The most frequent signs included conjunctival injection (n = 18, 62%), superficial punctate keratitis (n = 16, 55%), and papillary reaction (n = 8, 28%). Topical corticosteroids (TCS) (n = 23, 79%), tacrolimus (n = 6, 21%), and artificial tears (n = 7, 24%) were the most commonly used therapies. Of those with follow-up documentation (n = 21), 20 were noted to have partial or complete response with TCS based on symptoms and reduction of signs. Using our proposed symptom-based grading scale, scaled 1 to 5 based on the presence of common symptoms listed above, 66% (n = 19) requiring topical immunomodulating therapy were found in the 'severe' group (≥3 symptoms) and 17% (n = 5) were found in the 'mild' group (≤2 symptoms). CONCLUSIONS: This study provides insight into the commonly presenting ocular signs and symptoms associated with DAOSD and highlights the efficacy of TCS and other immunomodulators in improving symptoms associated with DAOSD. Based on our findings, we propose a symptom-based grading system that can guide nonophthalmic physicians regarding ophthalmology consult.

Cannabis and the Cornea.

Purpose: While cannabis has the potential to reduce corneal pain, cannabinoids might induce side effects. This review article examines the effects of cannabinoids on the cornea. As more states and countries consider the legalization of adult cannabis use, health-care providers will need to identify ocular effects of cannabis consumption.Methods: Studies included in this review examined the connection between cannabis and the cornea, more specifically anti-nociceptive and anti-inflammatory actions of cannabinoids. NCBI Databases from 1781 up to December 2019 were consulted.Results: Five studies examined corneal dysfunctions caused by cannabis consumption (opacification, decreased endothelial cell density). Twelve studies observed a reduction in corneal pain and inflammation (less lymphocytes, decreased corneal neovascularization, increased cell proliferation and migration).Conclusion: More than half of the studies examined the therapeutic effects of cannabinoids on the cornea. As the field is still young, more studies should be conducted to develop safe cannabinoid treatments for corneal diseases.

Vitamin B12 deficiency evaluation and treatment in severe dry eye disease with neuropathic ocular pain.

PURPOSE: This study aims to understand the effect of vitamin B12 deficiency on neuropathic ocular pain (NOP) and symptoms in patients with dry eye disease (DED). METHODS: Patients with severe DED (without receiving topical artificial tears treatment) and ocular pain were enrolled (n = 90). Patients with severe DED and vitamin B12 deficiency (group 1, n = 45) received parenteral vitamin B12 supplement + topical treatment (artificial tears treatment + cyclosporine), and patients with severe DED and normal serum vitamin B12 level (group 2, n = 45) received only topical treatment (artificial tears treatment + cyclosporine). Patients were evaluated by the ocular surface disease index (OSDI) questionnaire, 3rd question (have you experienced painful or sore eyes during last week?) score of OSDI as a pain determiner and pain frequency measure), tear break up time (TBUT), and Schirmer's type 1 test. We compared the groups' OSDI, TBUT, and Schirmer's test recordings at the first visit and after 12 weeks retrospectively. RESULTS: The OSDI score, 3rd OSDI question score, TBUT, and Schirmer's test results improved after 12 weeks (p < 0.001 for each group). The mean vitamin B12 level at enrollment was 144.24 ±43.36 pg/ml in group 1 and 417.53 ±87.22 pg/ml in group 2. The mean vitamin B12 level in group 1 reached to 450 ±60.563 pg/ml after 12 weeks of treatment. The mean score changes between the groups were not statistically significant; however, the decrease in the OSDI questionnaire score (-30.80 ±5.24) and 3rd OSDI question score (-2.82 ±0.53) were remarkable in group 1 (Table 2). The mean TBUT increase was +7.98 ±2.90 s and Schirmer's test result increase was +12.16 ±2.01 mm in group 1. The mean TBUT increase was +6.18 ±1.49 s and Schirmer's test result increase was +6.71 ±1.47 mm in group 2. CONCLUSIONS: These findings indicate that vitamin B12 deficiency is related with NOP. It may be important to consider measuring the serum vitamin B12 level in patients with severe DED presenting with resistant ocular pain despite taking topical treatment.

A Comparative Study Between an Oil-in-Water Emulsion and Nonlipid Eye Drops Used for Rewetting Contact Lenses.

OBJECTIVES: The purpose of this study was to determine the clinical impact of using SYSTANE BALANCE Lubricant Eye Drops (Alcon, Fort Worth, TX), an oil-in-water emulsion, as a rewetting eye drop in symptomatic contact lens wearers. METHODS: Subjects who had previously experienced contact lens discomfort (CLD), with a mean lens wearing history of 18.6±12.8 years, were randomly assigned to use a Test (SYSTANE BALANCE Lubricant Eye Drops; n=76) or control (habitual nonlipid contact lens rewetting eye drop; n=30) drop over their contact lenses within 5 min of lens insertion and then subsequently at 2 hr intervals up to a maximum of 4 drops per eye daily for a 1-month period. Assessments of subjective comfort, comfortable wearing time, lid wiper epitheliopathy (LWE), and corneal staining were conducted at baseline and after 1 month, after 6 hr of lens wear. RESULTS: Comfort, wearing time, LWE, and corneal staining all showed statistically significant improvements in the test group using SYSTANE BALANCE Lubricant Eye Drops at the 1-month visit compared with baseline data (all P<0.01) and compared with the control group at the 1-month visit (P<0.01, P=0.01, P<0.01, and P=0.03, respectively). CONCLUSIONS: The use of SYSTANE BALANCE Lubricant Eye Drops as a rewetting drop in a group of wearers who experienced symptoms of CLD improved subjective comfort scores, increased comfortable wearing time, and reduced signs of LWE and corneal staining, when compared with the use of non-lipid-containing contact lens rewetting eye drops.

Management of Ocular Neuropathic Pain With Vitamin B12 Supplements: A Case Report.

PURPOSE: To report the case of a 28-year-old patient with persistent bilateral burning pain and foreign body sensation in both eyes for the past 1 year. The patient showed a poor response to 0.05% cyclosporine eye drops and frequent instillations of artificial tears. Ocular examination showed few superficial punctate epithelial defects, well-positioned laser in situ keratomileusis (performed 5 years ago with symptomless recovery) flaps, and clear interfaces bilaterally, with a tear film breakup time of 7 and 8 seconds in the right and left eyes, respectively. The results of Schirmer tests, confocal microscopy, corneal esthesiometry, and meibography were normal for both eyes. The patient was incidentally diagnosed with vitamin B12 deficiency, with a serum vitamin B12 value of 90 pg/mL (reference range, 236-911 pg/mL), during routine laboratory tests. In view of weak correlation between signs and symptoms, a putative diagnosis of ocular neuropathic pain secondary to vitamin B12 deficiency was made. METHODS: Case report. RESULTS: The patient was treated with parenteral vitamin B12, and topical therapy was continued without any changes. The patient experienced dramatic improvement with a decrease in symptoms within 3 weeks of administering vitamin B12 supplements and was symptom-free in the absence of any topical medication 6 months after treatment. CONCLUSIONS: Vitamin B12 deficiency, although common in India, has not been reported to be associated with ocular symptoms, including pain and mimicking those seen in severe dry eye. Vitamin B12 deficiency should be considered in the differential diagnosis of ocular neuropathic pain and dry eye in patients presenting with recalcitrant ocular neuropathic pain.

Ocular damage secondary to intense pulse light therapy to the face.

PURPOSE: To promote awareness and prevention of ocular damage that can occur during Intense Pulsed Light (IPL) treatments of the periocular areas. METHODS: A retrospective chart review was conducted of 2 cases involving ocular damage following IPL procedures that were treated at Bascom Palmer Eye Institute for ocular complications. Routine data were collected during ophthalmic examinations. RESULTS: Case 1: A 36-year-old female presented with eye pain, marked pupillary constriction, and anterior uveitis an hour after receiving IPL treatment to the face. Within 1 month, the damage had progressed to posterior synechiae and iris transillumination defects. She continues to have pain and severe photophobia due to permanent iris atrophy and transillumination that have persisted for years. Case 2: A 27-year-old female presented with severe eye pain, vision disturbances, pupillary defects, and anterior uveitis 3 days after IPL of an eyelid freckle. At 2 months follow up, the iris and pupillary defects remain permanent. The patient continues to suffer from photophobia and pain. CONCLUSIONS: The pigmented iris absorbs light in the same wavelength range of IPL, thus remaining vulnerable to IPL exposure, especially when applied to the periocular area. The fact that IPL is not a laser may give people a false sense of security regarding damage to the eye. The cases presented give evidence that periorbital IPL treatment may permanently affect pigmented intraocular structures. It is imperative for treating physicians to be aware of these hazards and to use appropriate eye protection to prevent ocular damage.