Current Advances in Mechanisms and Treatment of Dry Eye Disease: Toward Anti-inflammatory and Immunomodulatory Therapy and Traditional Chinese Medicine

Dry eye is currently one of the most common ocular surface disease. It can lead to ocular discomfort and even cause visual impairment, which greatly affects the work and quality of life of patients. With the increasing incidence of dry eye disease (DED) in recent years, the disease is receiving more and more attention, and has become one of the hot research fields in ophthalmology research. Recently, with the in-depth research on the etiology, pathogenesis and treatment of DED, it has been shown that defects in immune regulation is one of the main pathological mechanisms of DED. Since the non-specific and specific immune response of the ocular surface are jointly regulated, a variety of immune cells and inflammatory factors are involved in the development of DED. The conventional treatment of DED is the application of artificial tears for lubricating the ocular surface. However, for moderate-to-severe DED, treatment with anti-inflammatory drugs is necessary. In this review, the immunomodulatory mechanisms of DED and the latest research progress of its related treatments including Chinese medicine will be discussed.

New Perspectives in the Pathophysiology and Treatment of Pain in Patients with Dry Eye Disease

Ocular discomfort and eye pain are frequently reported by patients with dry eye disease (DED), and their management remains a real therapeutic challenge for the Ophthalmologist. In DED patients, injury at the level of each structure of the ocular surface can determine variable symptoms, ranging from mild ocular discomfort up to an intolerable pain evoked by innocuous stimuli. In refractory cases, the persistence of this harmful signal is able to evoke a mechanism of maladaptive plasticity of the nervous system that leads to increased pain responsiveness. Peripheral and, subsequently, central sensitization cause nociceptor hyperexcitability and persistent pain perception that can culminate in the paradoxical situation of perceiving eye pain even in the absence of ocular surface abnormalities. Effective therapeutic strategies of these cases are challenging, and new options are desirable. Recently, a theoretical novel therapeutic approach concerns enkephalins thanks to the evidence that eye pain sensations are modulated by endogenous opioid peptides (enkephalins, endorphins and dynorphins). In this regard, new topical agents open up a new theoretical scenario in the treatment of ocular discomfort and eye pain in the setting of DED, such as, for example, a multimolecular complex based on proteins and glycosaminoglycans also containing opiorphin that may assist the physiological pain-relieving mechanism of the eye.

Systemic Treatment of Immune-Mediated Keratoconjunctivitis Sicca with Allogeneic Stem Cells Improves the Schirmer Tear Test Score in a Canine Spontaneous Model of Disease

Keratoconjunctivitis sicca (KCS) is characterized by ocular discomfort, conjunctival hyperaemia, and corneal scarring, causing reduced aqueous tear production that can be measured using the standard Schirmer tear test (STT). Canine adipose tissue-derived MSCs (cATMSCs) have been proposed as treatment due to their anti-inflammatory effect, by releasing cytokines and immunomodulatory soluble factors. Purpose: The aim of this study was to evaluate the effect of the systemic administration of cATMSCs on tear production in dogs with immune-mediated KCS, compared to classical Cyclosporine A (CsA) treatment. Methods: Twenty-eight client-owned dogs with spontaneous KCS were allocated in the experimental group (n = 14, treated with systemic cATMSCs or control group (n = 14, treated with CsA). SST values increased significantly at days 15 (p = 0.002), 45 (p = 0.042) and 180 (p = 0.005) with no observed side-effects in the experimental group. Eyes with an initial STT value of 11–14 mm/min maintained significant improvement at day 180, needing only artificial tears as treatment. Eyes with an initial STT value <11 mm/min needed cyclosporin treatment at day 45, so follow-up was stopped. Control animals treated with CsA did not improve their STT at day 180. Results and Conclusions: Systemic allogeneic cATMSCs application appeared to be a feasible and effective therapy with positive outcome in dogs with initial STT between 11–14 mm/min, with a significant improvement in tear production. The STT increment was maintained for at least 180 days, without needing additional medication, thus suggesting it could constitute an alternative therapy to classical immunosuppressive treatments.

Changes in Tear Osmolarity and Matrix Metalloproteinase-9 Relative to Ocular Discomfort after Femtosecond Laser-Assisted Cataract Surgery

The aim of this study was to evaluate the changes in tear osmolarity and matrix metalloproteinase-9 (MMP-9) and their relationships with ocular discomfort in patients after femtosecond laser-assisted cataract surgery (FLACS). This retrospective observational case series reviewed medical records of 51 eyes of 51 patients who underwent FLACS. Tear osmolarity and MMP-9 were evaluated preoperatively and at 1 day, 1 week, and 1 month postoperatively. Tear osmolarity ≥ 310 mOsm/L and MMP-9 ≥ trace positive were defined as abnormal results. The ocular surface disease index (OSDI) was evaluated preoperatively and postoperatively at 1 month. Tear osmolarity level and the number of eyes with abnormal tear osmolarity results did not change significantly up to 1 month after surgery. MMP-9 level and the number of eyes with abnormal MMP-9 results increased at 1-day postoperatively and then decreased at 1-month postoperatively (all p < 0.001). Among the OSDI subscales, ocular discomfort was aggravated (p < 0.001) but the visual function score improved at 1 month postoperatively (p < 0.001). Ocular discomfort aggravated after FLACS without an increase in either tear osmolarity or MMP-9. Ocular discomfort which patients commonly experience after FLACS may be due to etiology other than development or aggravation of dry eye disease.

Non-Toxic Anesthesia for Cataract Surgery

Background: To study the safety and efficacy provided by a minimal and localized anesthesia in cataract surgery. Methods: Randomized controlled trial. A total of 100 patients undergoing cataract surgery were randomly divided into two groups of 50, which respecitvely received conventional topical anesthesia consisting of preservative-free Oxibuprocaine hydrochloride 0.4% drops or minimal localized anesthesia, administered with a cotton bud soaked in preservative-free Oxibuprocaine hydrochloride 0.4% applied to clear cornea on the access sites for 10 s immediately before surgery. The mean outcome measures were intraoperative pain and the incidence of postoperative ocular discomfort. Results: All patients tolerated well the procedure, giving patin scores between 1–3. Fifteen patients (30%) of group 1 and ten of group 2 (25%) required supplemental anesthesia. No intraoperative complications were recorded. No eyes had epithelial defects at the end of the surgery or at postoperative check-ups. Conclusions: Minimal anesthesia in cataract surgery resulted quick, safe and non-invasive.

Deciphering the Action of Perfluorohexyloctane Eye Drops to Reduce Ocular Discomfort and Pain

Perfluorohexyloctane (F6H8) eyedrops have been recently introduced in Europe as a product to treat dry eye disease, based on its ability to reduce tear film instability in Meibomian gland dysfunction and evaporative dry eye disease, although its mechanism of action is still unknown. In the present pilot study, we evaluated the effects of the ocular instillation of a single drop of commercial F6H8 eyedrops in 20 healthy humans (9 women/11 men), measuring: (a) Corneal surface temperature (CST) from infrared video images; (b) tear volume using phenol red threads; (c) blinking frequency; and (d) ocular surface sensations (cold, dryness, pricking, foreign body, burning, itching, gritty, eye fatigue, watering eyes, and light-evoked discomfort sensations; scored using 10 cm Visual Analog Scales), before and 5–60 min after F6H8 or saline treatment. CST decreased and tearing and blinking frequency increased significantly after F6H8 but not after saline solution. When applied unilaterally, CST decreased only in the F6H8-treated eye. No sensations were evoked after F6H8 or saline. The corneal surface temperature reduction produced by topical F6H8 does not evoke conscious ocular sensations but is sufficient to increase the activity of corneal cold thermoreceptors, leading to an increased reflex lacrimation and blinking that may relieve dry eye condition thus reducing ocular discomfort and pain.

Contact Lens-Associated Infectious Keratitis: Update on Diagnosis and Therapy

The focus of this chapter is to review the most recent advances in the diagnosis and treatment of contact-lens-related infectious keratitis, the most sight-threatening complication of contact lens wear. In the last decades, contact lenses technology has confronted several challenges, including the need for safer and more comfortable polymer materials. The development of high coefficient oxygen permeability (Dkt) and low-water content disposable contact lens translated into a significant improvement in ocular discomfort related to dry eye and allergic reactions, decreasing biofilm build-up on the external surface of the lens. Additionally, the emergence and boom-effect of corneal refractive surgery have also driven the development of better contact lens manufacturing. Despite these substantial technological advances, contact lens users continue to be at risk for developing corneal infections. We describe recent epidemiologic data, and advances in understanding the complex pathogenesis of the disease, including the clinical characteristics of the infectious process produced by bacteria, fungi, and protozoans. Finally, the recent development of diagnostic techniques and therapeutic regimens are discussed.

Computer vision syndrome: a rising problem during COVID-19 period amongst students and online workers

Dear Editor, Computer vision syndrome (CVS) is defined as complex eye discomfort and vision problems associated with prolonged exposure to digital screens.1 Symptoms include headache, dry eyes, eye strain, blurring of vision, and ocular discomfort after prolonged exposure to light from computers.2,3 Blue light filtering lenses can be used to minimize CVS.2 Globally, around 70 million workers are at risk for computer vision syndrome which reduces the quality of life and work productivity.1 In the western world, use of computers, for both vocational and non-vocational activities, is almost mandatory.1 In today's COVID-19 (Corona-Virus Disease - 2019) era, use of computers and other digital screen devices is surging in Nepal as well, especially for online study and work from home to control the further spread of coronavirus. Moreover, the lockdown and shutdown done for the virus control by minimizing human gathering increase the demand for virtual learning and working through the online medium.

PREVALENCE AND RISK FACTORS OF DRY EYE AMONG PATIENTS OF A TERTIARY CARE CENTRE IN EASTERN INDIA

AIM: To determine the prevalence and risk factors of dry eye among patients of a tertiary care centre in eastern India. Symptoms of dry eye are encountered as one of the most frequent complains among the patients attending the outpatient department in ophthalmology commonly presenting as ocular discomfort, burning sensation and foreign body sensation.Prevalence of this entity is still not known in our study population due to lack of specificity of symptoms and diagnostic criteria. MATERIALS AND METHODS: A prospective, observational, cross-sectional study was conducted among patients attending ophthalmology OPD in a tertiary care teaching hospital of Bihar. 4116 (16.64%) patients with dry eye symptoms were examined after taking informed consent. RESULTS: 1620 (6.55%) patients were found to have dry eye based on McMonnies questionnaire, Schirmer's test and tear film breakup time.There were 1180 female and 440 male with dry eye.Male to female ratio was 2.7:1.Non-tribals were affected more commonly than tribals. Students, outdoor workers and office worker with professional constituted over fifty percent of dry eye cases. CONCLUSION: Prevalence of dry eye was more in females and elderly as compared to male and younger population respectively.Burning sensation and ocular discomfort was the most common presenting complains.

Role of artificial tears with and without hyaluronic acid in controlling ocular discomfort following PRK: a randomized clinical trial

AIM: To compare outcomes of applying preservative free artificial tears (PFAT) with and without hyaluronic acid (HA) in early postoperative course following photorefractive keratectomy (PRK). METHODS: In this triple-blinded randomized clinical trial, PRK procedure was performed on both eyes of 230 patients. Following PRK, patients were divided into three groups: the HA+ group, 44 patients PFAT containing HA; the HA- group, 71 patients PFAT without HA were administered 5 times per day (every 4h); the third group, 115 patients received no PFAT before lens removal. On the 1st and 4th postoperative day, Visual Analogue Score (VAS) was utilized to evaluate patient’s level of pain. Participants were asked to complete a questionnaire about the severity of eye discomfort ranked from 0 to 10 (0=no complaint; 10=most severe complaint experienced). RESULTS: In eyes receiving PFAT with or without HA (Drop group), mean scores for epiphora, foreign body sensation, and blurred vision on the 1st postoperative day were statistically lower (P<0.05). Filamentous keratitis (FK) was detected in 11 (4.7%) eyes, and recurrent corneal erosion (RCE) was observed in 5 (2.1%) eyes. In the control group, FK was noted in 16 (6.9%) eyes while 13 (5.6%) eyes had RCE and 5 (2.1%) eyes had corneal haze. The rate of complications was statistically lower in Drop group (P=0.009). However, the aforementioned scores were not statically different between HA+ and HA- group one and two (P=0.29). CONCLUSION: Following PRK, applying PFAT with and without HA yields faster visual recovery, decreases postoperative ocular discomfort and haze formation; however there is no additive effect for HA.