Differential effects of obstructive sleep apnea on the corneal subbasal nerve plexus and retinal nerve fiber layer.

PURPOSE: Obstructive sleep apnea (OSA) is an established independent risk factor for peripheral neuropathy. Macro and microvascular changes have been documented in OSA, including high levels of potent vasoconstrictors. In diabetes, vasoconstriction has been identified as an underlying risk factor for corneal neuropathy. This study sought to establish a potential relationship between OSA and corneal nerve morphology and sensitivity, and to determine whether changes in corneal nerves may be reflective of OSA severity. DESIGN: Single center cross-sectional study. METHODS: Sixty-seven patients were stratified into two groups: those with OSA and healthy controls. Groups were matched for age, sex, race, smoking, and dry eye status. Outcome measures included serologies, a dilated fundus exam, dry eye testing, anthropometric parameters, corneal sensitivity, subbasal nerve plexus morphology, retinal nerve fiber layer (RNFL) thickness, and the use of questionnaires to assess symptoms of dry eye disease, risk of OSA, and continuous positive airway pressure (CPAP) compliance. RESULTS: No significant differences were observed in corneal nerve morphology, sensitivity, or the number of dendritic cells. In the OSA test group, RNFL thinning was noted in the superior and inferior regions of the optic disc and peripapillary region. A greater proportion of participants in the OSA group required a subsequent evaluation for glaucoma than in the control. In those with OSA, an increase in the apnea hypopnea index was associated with an increase in optic nerve cupping. CONCLUSIONS: OSA does not exert a robust effect on corneal nerves. OSA is however, associated with thinning of the RNFL. Participants with glaucomatous optic nerve changes and risk factors for OSA should be examined as uncontrolled OSA may exacerbate glaucoma progression.

Progesterone Application to the Rat Forehead Produces Corneal Antinociception.

Purpose: Ocular pain and discomfort are the most defining symptoms of dry eye disease. We determined the ability of topical progesterone to affect corneal sensitivity and brainstem processing of nociceptive inputs. Methods: Progesterone or vehicle gel was applied to the shaved forehead in male Sprague Dawley rats. As a site control, gel also was applied to the cheek on the side contralateral to corneal stimulation. Corneal mechanical thresholds were determined using the Cochet-Bonnet esthesiometer in intact and lacrimal gland excision-induced dry eye animals. Eye wipe behaviors in response to hypertonic saline and capsaicin were examined, and corneal mustard oil-induced c-Fos immunohistochemistry was quantified in the brainstem spinal trigeminal nucleus. Results: Progesterone gel application to the forehead, but not the contralateral cheek, increased corneal mechanical thresholds in intact and lacrimal gland excision animals beginning <30 minutes after treatment. Subcutaneous injection of the local anesthetic bupivacaine into the forehead region before application of progesterone prevented the increase in corneal mechanical thresholds. Furthermore, progesterone decreased capsaicin-evoked eye wipe behavior in intact animals and hypertonic saline evoked eye wipe behavior in dry eye animals. The number of Fos-positive neurons located in the caudal region of the spinal trigeminal nucleus after corneal mustard oil application was reduced in progesterone-treated animals. Conclusions: Results from this study indicate that progesterone, when applied to the forehead, produces analgesia as indicated by increased corneal mechanical thresholds and decreased nociceptive responses to hypertonic saline and capsaicin.

Intense pulsed light treatment and meibomian gland expression for moderate to advanced meibomian gland dysfunction.

BACKGROUND: The aim was to evaluate the efficacy of periocular intense pulsed light therapy combined with meibomian gland expression for chronic dry eye due to moderate to advanced meibomian gland dysfunction. METHODS: This single-institution, open-label prospective study involved 26 participants who received bilateral treatments using a proprietary intense pulsed light device (E > Eye, E-Swin, Paris, France) combined with therapeutic meibomian gland expression at baseline, Week 2 and Week 6. Clinical evaluations performed at baseline, Week 4, Week 8 and Week 12 were symptom scores (Ocular Surface Disease Index [OSDI], Ocular Comfort Index [OCI], daily lubricant use, tear break-up time and ocular surface staining). Tear secretion, tear osmolarity, InflammaDry tear immunoassay, corneal sensation, meibomian secretion quality and expressibility, bulbar conjunctival, limbal and lid margin redness and eyelid margin bacterial swab for cultures and colony counts were performed at baseline and Week 8 only. RESULTS: Significant improvements occurred at Week 8 in meibomian gland expressibility (p = 0.002), meibum quality (p = 0.006), tear break-up time (p = 0.002), corneal staining (p = 0.001), lid margin redness (p = 0.001), bulbar redness (p = 0.05) and limbal redness (p = 0.001). Symptom survey outcomes, eyelid margin bacteria colony counts, Schirmer I test, tear osmolarity, corneal sensitivity and daily lubricant use were unchanged. At Week 12, significant improvements in symptoms (OSDI p = 0.025; OCI p = 0.003), tear break-up time (p = 0.001) and corneal staining (p = 0.001) occurred. Improvement in OSDI score was correlated to the improvement in ocular surface staining (R = 0.43, p = 0.03) and associated with baseline meibomian gland expressibility (Kendall tau: the distributions are ordered the same, p = 0.1). There were no adverse effects of treatment. CONCLUSIONS: Serial intense pulsed light therapy combined with meibomian gland expression significantly improved dry eye symptoms and clinical signs, including meibomian gland secretion quality and expressibility and ocular surface inflammation. Treatment effects were cumulative and sustained for at least six weeks after the final treatment.

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 Randomized Controlled Trial of Omega 3 Fatty Acids in Rosacea Patients with Dry Eye Symptoms.

Objective or purpose: To evaluate the efficacy of dietary omega-3 fatty acids (O3FAs) in rosacea patients having dry eye symptoms. METHODS: A prospective, interventional, randomized, double-masked, placebo-controlled, multi-centric study was done. Symptomatic patients with rosacea were recruited based on their response to (Dry Eye Scoring System, DESS©); a score of 0-3 was assigned to dry eye-related symptoms like ocular fatigue, blurring of vision, itching or burning, sandy or gritty sensation, and redness, respectively (DESS©). Subjects were (n = 130) were randomized to receive either O3FAs (n = 65) or placebo (n = 65) capsules (olive oil) twice daily for 6 months. Patients were evaluated at baseline, 1, 3, and 6 months. Change in subjective dry eye symptoms was the primary outcome measure. Change in meibomian gland score (MGS), Schirmer score, and tear film breakup time (TBUT) were the secondary outcome measures. RESULTS: Repeated-measures ANOVA revealed that there was a significant (p < 0.001) change in symptoms (F(1.506, 88.825 = 315.193), MGS (F(1.336, 78.796 = 84.438), Schirmer score (F(1.322, 78.022 = 86.559), and TBUT (F(1.354, 79.898 = 179.020.559) in O3FA group as compared to placebo group. Post-hoc test revealed that there was a significant change in dry eye symptoms at all points of time; there was a significant change in MGS, Schirmer score, and TBUT also, but only after 3 months of intervention. Linear regression established that symptom severity could significantly predict MGS, Schirmer score, and TBUT. There was a significant change in the slope (intercept) of the regression plots in O3FA group as compared to the placebo group. CONCLUSION: Rosacea patients with dry eye symptoms have significant improvement in symptoms, MGS, TBUT, and Schirmer score, following dietary intervention with O3FAs for 6 months.

Inflammation and keratoconus.

Keratoconus (KC) has been traditionally classified as a noninflammatory disease. Barring loss of function, the other classic signs of inflammation (heat, redness, swelling, pain) are not usually obvious or even apparent in KC. This clinical perspective examines the evidence and implications of numerous inflammatory processes that have been recognized in the tears of KC patients as well as some inflammation relevant differences found in the KC cornea. The roles of inflammation in corneal trauma attributed to eye rubbing and/or contact lens wear are examined as is the significance of atopy, allergic disease, dry eye disease, degradative enzyme activity, wound healing, reduced anti-inflammatory capacity, and ultraviolet irradiation. It is possible that any comorbidity that is inflammatory in nature may add synergistically to other forms of KC-related inflammation and exacerbate its pathogenetic processes. For example, some features of inflammation in ocular rosacea and associated corneal thinning and distortion could have some possible relevance to KC. An analogy is drawn with osteoarthritis, which also involves significant inflammatory processes but, like KC, does not meet all the classic criteria for an inflammatory disease. Classifying KC as quasi-inflammatory (inflammatory-related) rather than a noninflammatory disease appears to be more appropriate and may help focus attention on the possibility of developing effective anti-inflammatory therapies for its management.

Comparison of treatment with preservative-free versus preserved sodium hyaluronate 0.1% and fluorometholone 0.1% eyedrops after cataract surgery in patients with preexisting dry-eye syndrome.

PURPOSE: To compare treatment with preservative-free and preserved sodium hyaluronate 0.1% and fluorometholone 0.1% eyedrops after cataract surgery in patients with preexisting dry-eye syndrome. SETTING: Bucheon St. Mary's Hospital, Catholic University of Korea, Seoul, Korea. DESIGN: Randomized controlled study. METHODS: Patients with cataract and dry-eye syndrome were randomly divided into 2 groups. Group 1 patients were treated with preservative-free sodium hyaluronate 0.1% and preservative-free fluorometholone 0.1% eyedrops 4 times a day in the first month and twice a day in the second month. Group 2 patients were treated with preserved eyedrops using the same schedule. Ocular Surface Disease Index (OSDI) score, tear-film breakup time (TBUT), Schirmer I test, corneal fluorescein staining, impression cytology, and antioxidant and inflammatory cytokine activities in tears were evaluated. RESULTS: Both groups comprised 40 patients. At 2 months, the OSDI score, TBUT, Schirmer I score, fluorescein staining score, impression cytology findings, and goblet cell count were significantly better in Group 1 than in Group 2 (P<.05). The interleukin-1ß and tumor necrosis factor-α concentrations were significantly less in the tears of Group 1 patients than in the tears of Group 2 patients, and catalase and superoxide dismutase 2 fluorescence intensities were significantly greater in the tears of Group 1 patients than in the tears of Group 2 patients (P<.05). CONCLUSIONS: Preservative-free sodium hyaluronate 0.1% and fluorometholone 0.1% eyedrops can improve the symptoms and signs of dry-eye syndrome after cataract surgery. Preservative-free fluorometholone eyedrops may have antiinflammatory and antioxidant effects in tears of patients with dry-eye syndrome. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Randomised masked clinical trial of the MGDRx EyeBag for the treatment of meibomian gland dysfunction-related evaporative dry eye.

BACKGROUND/AIMS: To investigate the efficacy and safety of the MGDRx EyeBag (The Eyebag Company, Halifax, UK) eyelid warming device. METHODS: Twenty-five patients with confirmed meibomian gland dysfunction (MGD)-related evaporative dry eye were enrolled into a randomised, single masked, contralateral clinical trial. Test eyes received a heated device; control eyes a non-heated device for 5 min twice a day for 2 weeks. Efficacy (ocular symptomology, non-invasive break-up time, lipid layer thickness, osmolarity, meibomian gland dropout and function) and safety (visual acuity, corneal topography, conjunctival hyperaemia and staining) measurements were taken at baseline and follow-up. Subsequent patient device usage and ocular comfort was ascertained at 6 months. RESULTS: Differences between test and control eyes at baseline were not statistically significant for all measurements (p>0.05). After 2 weeks, statistically significant improvements occurred in all efficacy measurements in test eyes (p<0.05). Visual acuity and corneal topography were unaffected (p>0.05). All patients maintained higher ocular comfort after 6 months (p<0.05), although the benefit was greater in those who continued usage 1-8 times a month (p<0.001). CONCLUSIONS: The MGDRx EyeBag is a safe and effective device for the treatment of MGD-related evaporative dry eye. Subjective benefit lasts at least 6 months, aided by occasional retreatment. TRIAL REGISTRATION NUMBER: NCT01870180.

Dry age-related macular degeneration: mechanisms, therapeutic targets, and imaging.

Age-related macular degeneration is the leading cause of irreversible visual dysfunction in individuals over 65 in Western Society. Patients with AMD are classified as having early stage disease (early AMD), in which visual function is affected, or late AMD (generally characterized as either "wet" neovascular AMD, "dry" atrophic AMD or both), in which central vision is severely compromised or lost. Until recently, there have been no therapies available to treat the disorder(s). Now, the most common wet form of late-stage AMD, choroidal neovascularization, generally responds to treatment with anti-vascular endothelial growth factor therapies. Nevertheless, there are no current therapies to restore lost vision in eyes with advanced atrophic AMD. Oral supplementation with the Age-Related Eye Disease Study (AREDS) or AREDS2 formulation (antioxidant vitamins C and E, lutein, zeaxanthin, and zinc) has been shown to reduce the risk of progression to advanced AMD, although the impact was in neovascular rather than atrophic AMD. Recent findings, however, have demonstrated several features of early AMD that are likely to be druggable targets for treatment. Studies have established that much of the genetic risk for AMD is associated with complement genes. Consequently, several complement-based therapeutic treatment approaches are being pursued. Potential treatment strategies against AMD deposit formation and protein and/or lipid deposition will be discussed, including anti-amyloid therapies. In addition, the role of autophagy in AMD and prevention of oxidative stress through modulation of the antioxidant system will be explored. Finally, the success of these new therapies in clinical trials and beyond relies on early detection, disease typing, and predicting disease progression, areas that are currently being rapidly transformed by improving imaging modalities and functional assays.

Patients undergoing long-term treatment with antihypertensive eye drops responded positively with respect to their ocular surface disorder to oral supplementation with antioxidants and essential fatty acids.

BACKGROUND: Glaucoma and dry eye disorders (DEDs) are frequent comorbidities. The antioxidant and anti-inflammatory properties of essential polyunsaturated fatty acids have been extensively studied in relation to eye diseases. OBJECTIVE: Our objective was to determine the effects of oral supplementation with a combined formulation of antioxidants and essential polyunsaturated fatty acids on expression of cytokines and chemokines in tears from patients with DEDs or primary open-angle glaucoma (POAG). METHODS: Participants (n = 97) were distributed into three groups: (1) individuals with nonsevere DEDs (DEDG), (2) individuals with nonadvanced POAG (POAGG), and (3) healthy controls. These groups were randomized into two subgroups: one received a daily antioxidant and essential polyunsaturated fatty acid supplement (two pills) for 3 months (+S), and the other did not (-NS). Participants were interviewed and ophthalmologically examined. Concentrations of specific cytokines and chemokines in reflex tears were determined by multiplexed particle-based flow cytometry. The data were analyzed statistically (SPSS version 15.0). RESULTS: Comparison of the results from the DEDG and POAGG patients showed significant differences in tear expression of granulocyte-macrophage colony-stimulating factor (P = 0.008), tumor necrosis factor α (P = 0.005), vascular endothelial growth factor (P = 0.038), interleukin-4 (P = 0.030), and interleukin-6 (P = 0.044). The main signs and symptoms of dry eyes such as dryness, burning, photophobia, eye heaviness, and blurred vision, as well as positive changes in eyelashes, hair, nails and skin, were significantly improved in DEDG +S and POAGG +S patients relative to unsupplemented patients. CONCLUSION: Inflammation biomarkers were differentially expressed in glaucomatous tears, but the differences changed upon antioxidant/essential polyunsaturated fatty acid supplementation. Chronic instillation of antihypertensive eye drops must be considered for integrating protocols to glaucoma standards of care.

[Efficacy of lid hygiene in treatment of patients with blepharoconjunctival form of dry eye syndrome].

A complex of measures for lid hygiene in ocular surface disease is developed. These measures together with tear substitution and antibacterial treatment were revealed to result in elimination of blepharoconjunctivitis and dry eye signs, recovery of tear film and long-time remission, that significantly improved patient's life quality. When using this complex of measures meibomian glands are not damaged and their anatomy and functions are completely preserved. Lid hygiene affects all glands, there is no pain and no local anesthesia needed, normal tear film is formed

Xerophthalmia and intracranial hypertension in an autistic child with vitamin A deficiency.

The authors present a 10-year-old boy with autism and idiopathic intracranial hypertension referred for evaluation of dry eyes. When questioned, the patient's parents reported that he had a restricted diet. Laboratory testing revealed hypovitaminosis A. The symptoms and signs of xerophthalmia rapidly resolved with oral and topical vitamin A supplementation.

Is acupuncture an useful tool for pain-treatment in ophthalmology?

Pain that does not respond to conventional treatment procedures makes it necessary to look for alternative methods. Acupuncture is an ancient procedure with empirical effects on pain. Previous studies established the increased output of messengers at neuronal junctions in spinal cord and hypothalamic locations, especially of endorphins which inhibit the perception of pain. We treated several painful symptoms with acupuncture and evaluated the outcome of the treatment. Patients with various kinds of therapy-refractory pain and patients in whom conventional treatment methods could not be applied were included in the study. The diagnoses included glaucoma. Tolosa-Hunt-Syndrome, ophthalmic migraine, blepharospasm, and dry eyes. In one case acupuncture was used for analgesia during surgery. Acupuncture was performed with sterile disposable needles, at points known to have an empirical analgesic effect. The stimulation was adapted to the patient's individual needs. VAS assessments before and after acupuncture were compared. The t-test was used for statistical evaluation. Acupuncture had no side effects, but reduced pain to a variable extent. Especially in cases of severe pain and in surgery, very effective pain reduction was achieved. In general, pain was significantly reduced in all patients by the use of acupuncture. A statistically significant effect was noted (p < 0.05). Further studies should be conducted to demonstrate the specific effect in larger patient populations. Monitoring neurotransmitter activity will possibly help to illustrate the effect.

Mucus fishing syndrome: case report and new treatment option.

BACKGROUND: Mucus fishing syndrome (MFS) is a cascading cyclic condition characterized by continuous extraction of mucous strands from the eye. It is usually initiated by ocular irritation. In response to irritation, ocular surface cells produce excess mucus. A "snow balling" cycle begins when the patient extracts ("fishes") excess mucus from the ocular surface, thereby causing further irritation and a more-profound mucous discharge. To date, treatment includes eliminating the initiating element and educating the patient not to touch the eye when extracting the excess mucus, CASE REPORT: Presented is a case of mucus fishing syndrome initiated by dry eye. The patient's diagnosis, MFS, was identified by persistent mucous discharge, his admittance and demonstration of digitally extracting mucus from the ocular surface, and a characteristic rose bengal staining pattern. The conventional treatment initiated by using artificial tears for the dry eye condition and educating the patient not to touch the ocular surface did not provide relief from the excess mucous discharge. Therefore, a new approach to treatment was pursued. In order to break the cycle, a mucolytic agent and an antihistamine-mast cell stabilizer were prescribed, until the ocular surface healed. After treatment, the patient reported alleviation of symptoms and demonstrated improvement in ocular surface integrity by a profound reduction in rose bengal staining. CONCLUSION: Mucus fishing syndrome is challenging to resolve with conventional treatment because it requires a certain level of psychological tolerance and perseverance from the patient. By eliminating the present mucus and diminishing mucous production pharmacologically, the practitioner is able to remove the stimulus for digital extraction and thus accelerate ocular surface healing. We present a proposed new treatment option for patients who are refractory to conventional treatments.

Hydroxypropyl methylcellulose for the treatment of severe dry eye associated with Sjögren's syndrome.

Our purpose was to evaluate the efficacy of a new formulation of methylcellulose, preservative-free 0.5% hydroxypropyl methylcellulose (HPMC), for the treatment of dry eye. In the clinical part of our study, two groups of dry-eye patients, those with Sjögren's syndrome (SS) and those without (non-SS), were treated topically with 0.5% HPMC and evaluated for symptoms, ocular surface vital staining, tear breakup time (BUT), and tear evaporation rate from the ocular surface at 40% ambient humidity (TEROS40). In the in vivo part of the study, rose bengal uptake was measured in human conjunctival epithelial cells, which were cultured and incubated with or without 0.5% HPMC. Although symptoms improved in both groups, rose bengal and fluorescein staining and BUT improved significantly only in the SS group. TEROS40 increased for 30 min after instillation of 0.5% HPMC, but not after use of 0.1% sodium hyaluronate or saline-based artificial tears. Rose bengal uptake by cultured conjunctival epithelial cells was blocked by 0.5% HPMC. These findings suggest that 0.5% HPMC provides long coverage of and protection for the ocular surface. Patients with severe dry eye, such as in SS, are good candidates for this treatment.

Ojo seco / Dry eye

La deficiencia acuosa es la alteración más frecuente de la película lagrimal que determina ojo seco. A los síntomas clásicos de ardor, sensación de arenilla, fotofobia. etc., se agregan signos como disminución del menisco lagrimal, secreción mucosa, queratitis punctata, filamentos y otros, que junto a los colorantes vitales y exámenes específicos, hacen que el diagnóstico no sea problemático. Los pacientes más difíciles de tratar son los que presentan un síndrome de Sjögren, porque hay además un compromiso inmunológico. En ellas las lágrimas de sustitución, la oclusión de los puntos lagrimales, los mucolíticos, la vitamina A, la ciclosporina, etc., a veces no dan el resultado esperado y nos vemos obligados a realizar tarsorrafia, resección de conjuntiva o tratar de perforación corneal. Finalmente, es posible tener áreas de desecación si hay blefaropatías y/o irregularidades de la superficie ocular

Advanced xerophthalmia as a presenting sign in cystic fibrosis.

Xerophthalmia is a common complication of vitamin A deficiency in communities where malnutrition is found. We report on a 16-month-old infant with severe photophobia and failure to thrive. On examination, her major presenting sign was corneal xerosis, with corneal and conjunctival keratinization, and corneal stromal edema with opacification. Based on these findings, vitamin A deficiency secondary to fat malabsorption was suspected, and a workup confirmed the diagnosis of cystic fibrosis. With parenteral vitamin A supplementation, she had complete resolution of her ocular signs and symptoms. This case illustrates the value of a complete ophthalmic examination in the diagnosis of fat malabsorption syndromes.