A metabolomic approach to dry eye disorders. The role of oral supplements with antioxidants and omega 3 fatty acids.

PURPOSE: We used nuclear magnetic resonance spectroscopy of hydrogen-1 nuclei ((1)H NMR S) to analyze the metabolic profile of reflex tears from patients with dry eye disorders. METHODS: We performed a prospective case-control study involving 90 participants: 55 patients diagnosed with dry eye syndrome (DESG) and 35 healthy subjects (control group, CG). From the DESG, two subgroups were formed: mild DES (n=22) and moderate DES (n=33). Participants were prescribed an oral nutraceutic supplementation containing antioxidants and essential polyunsaturated fatty acids to be taken as three capsules per day for 3 months. Reflex tears (20-30 µl) were collected from the tear meniscus of both eyes of each subject with a microglass pipette. Nuclear magnetic resonance (NMR) spectra were acquired with a standard one-dimensional pulse sequence with water suppression; 256 free induction decays were collected into 64,000 data points with 14 ppm spectral width. RESULTS: Basal tears showed a differential metabolomic profile between groups. Almost 50 metabolites were identified by H cholesterol, N-acetylglucosamine, glutamate, amino-n-butyrate, choline, glucose, and formate were detected before supplementation and choline/acetylcholine after supplementation. The metabolic profile of the tears was statistically different between groups, as well as before and after supplementation. CONCLUSIONS: Our data indicate that DES induces changes in the tear metabolic profile that can be modified with appropriate oral supplementation with antioxidants and essential polyunsaturated fatty acids.

Differential effects of dry eye disorders on metabolomic profile by 1H nuclear magnetic resonance spectroscopy.

We used (1)H NMR spectroscopy to analyze the metabolomic profile of reflex tears from patients with dry eye disorders (DEDs). 90 subjects were divided into 2 groups: (1) patients with DEDs (DEDG; n = 55) and (2) healthy subjects (CG; n = 35). Additionally, the DEDG was subdivided into 2 subgroups based on DED severity: mild-to-moderate and moderate (n = 22 and n = 33, resp.). Personal interviews and systematized ophthalmologic examinations were carried out. Reflex tears (20-30 µL) were collected by gently rubbing in the inferior meniscus of both eyelids with a microglass pipette and stored at -80°C until analysis. NMR spectra were acquired using a standard one-dimensional pulse sequence with water suppression. Data were processed and transferred to MATLAB for further chemometric analysis. Main differences in tear composition between DEDG and CG were found in cholesterol, N-acetylglucosamine, glutamate, creatine, amino-n-butyrate, choline, acetylcholine, arginine, phosphoethanolamine, glucose, and phenylalanine levels. This metabolic fingerprint helped also to discriminate between the three additional subgroups of DEDG. Our results suggest that tear metabolic differences between DEDG and CG identified by NMR could be useful in understanding ocular surface pathogenesis and improving biotherapy.

Oxidative stress and its downstream signaling in aging eyes.

BACKGROUND: Oxidative stress (OS) and its biomarkers are the biochemical end point of the imbalance between reactive oxygen species (ROS) production and the ability of the antioxidant (AOX) biological systems to fight against oxidative injury. OBJECTIVE: We reviewed the role of OS and its downstream signaling in aging eyes. METHODS: A search of the literature and current knowledge on the physiological and pathological mechanisms of OS were revisited in relation to the eyes and the aging process. Most prevalent ocular diseases have been analyzed herein in relation to OS and nutraceutic supplements, such as dry-eye disorders, glaucoma, age-related macular degeneration, and diabetic retinopathy. RESULTS: Clinical, biochemical, and molecular data from anterior and posterior eye segment diseases point to OS as the common pathogenic mechanism in the majority of these ocular disorders, many of which are pathologies causing visual impairment, blindness, and subsequent loss of life quality. Studies with nutraceutic supplements in aging eye-related pathologies have also been reviewed. CONCLUSION: OS, nutritional status, and nutraceutic supplements have to be considered within the standards of care of older ophthalmologic patients. OS biomarkers and surrogate end points may help in managing the aging population with ocular diseases.

Ahmed valve, suture-less implantation: A new approach to an easier technique.

PURPOSE: Tissue adhesives have been used in ophthalmology instead of sutures to minimize the operating time. This case series investigated the effectiveness and safety of use of cyanoacrylate in Ahmed valve implantation through pars plana for refractory glaucoma. PATIENTS AND METHODS: Seventeen eyes of 17 patients with refractory glaucoma underwent Ahmed valve scleral suture-less implantation through pars plana with a cyanoacrylate suture of the plate. Refractory glaucoma was defined as intraocular pressure (IOP) ≥ 21 mm Hg with antiglaucoma eye drops, good adherence to treatment, and no previous glaucoma surgery. IOP control and development of complications were evaluated during the follow-up (mean follow-up, 13.23 mo, 6 to 28 mo). RESULTS: IOP control, defined as IOP ≤ 21 mm Hg with or without antiglaucoma eye drops, was achieved in 82.2% of patients, and 58.8% were able to eliminate antiglaucoma eye drops. Mean surgical time was 9.76 ± 2.60 and 6 ± 0.81 minutes in patients with previous vitrectomy (4 cases). Postoperative complications included transiently increased IOP, transient hyphema, early postoperative hypotony (4 cases), and tube block by the vitreous (2 cases): 1 resolved by Nd:YAG and the other by second vitrectomy. No cases of tube or plate extrusion, plate migration, choroidal or retinal detachment, or vitreous hemorrhage were observed. CONCLUSIONS: These results are promising and demonstrate a safe and effective alternative to the traditional scleral suture. Our data suggest that Ahmed valve implantation through pars plana with cyanoacrylate is a safe and effective method for refractory glaucoma. Further studies are needed to confirm our observation.

Update on the principles and novel local and systemic therapies for the treatment of non-infectious uveitis.

Ocular inflammatory disorders constitute a sight-threatening group of diseases that might be managed according to their severity. Their treatment guidelines experience constant changes with new agents that improve the results obtained with former drugs. Nowadays we can make use of a five step protocol in which topical, periocular and systemic corticosteroids remain as the main therapy for non-infectious uveitis. In addition, immunosuppresive drugs can be added in order to enhance the anti-inflammatory effects and to play the role of corticosteroid-sparing agents. These can be organized in four other steps: cyclosporine and methotrexate in a second one; azathioprine, mycophenolate and tacrolimus in a third step; biological anti-TNF drugs in fourth position; and a last one with cyclophosphamide and chlorambucil. In the present review we go through the main characteristics and complications of all these treatments and make a rational of this five-step treatment protocol for non-infectious posterior uveitis.

Ranibizumab for serous macular detachment in branch retinal vein occlusions.

BACKGROUND: The purpose of this study was to compare the efficacy of intravitreal ranibizumab in the treatment of macular edema due to branch retinal vein occlusions (BRVO) with and without serous macular neuroretinal detachment (SMD). METHODS: Forty-nine eyes of 49 patients with macular edema due to branch retinal vein occlusion (22 with SMD and 27 without SMD) were included in this prospective, parallel-group, comparative study. Intravitreal injection of ranibizumab was administered at baseline. Thereafter patients were followed monthly and further injections were performed in the presence of persistence or recurrence of macular thickening. Flattening of the macula was considered success. At the last visit, best-corrected visual acuity (BCVA), and spectral-domain optical coherence tomography (SD-OCT) quantitative parameters (central subfield thickness, cube volume, average cube thickness) were compared between groups. RESULTS: In patients with SMD, BCVA and all the SD-OCT quantitative parameters improved significantly after a mean number of 5.0 ranibizumab intravitreal injections through a median follow-up of 12.5 months (range, 7-34). In patients without SMD, all the variables analyzed improved significantly except for the cube volume, after a mean number of 4.3 ranibizumab intravitreal injections through a median follow-up of 10.4 months (range, 6.5-40.2). The numbers of injections were similar in both groups. The final BCVA was better in patients without SMD at baseline but without significant differences in the SD-OCT parameters between groups. CONCLUSIONS: The presence of SMD may be a baseline predictive factor for ranibizumab treatment outcomes in BRVO patients, with no influence in the number of treatments needed between patients with or without SMD at baseline. Further studies are needed in order to confirm the role of SMD as an independent predicitive factor in cases of BRVO.

Adult coats' disease successfully managed with the dexamethasone intravitreal implant (ozurdex®) combined with retinal photocoagulation.

PURPOSE: To report a case of Coats' disease managed with the dexamethasone intravitreal implant Ozurdex(®) (Allergan, Inc., Irvine, Calif., USA) combined with retinal photocoagulation. METHODS: A 46-year-old female with 20/200 visual acuity was diagnosed with Coats' disease with secondary retinal vasoproliferative tumor. An initial approach was performed with an intravitreal injection of the sustained-release dexamethasone implant Ozurdex. After reattachment of the retina, the telangiectatic vessels were treated with laser photocoagulation. RESULTS: The patient's visual acuity improved to 20/25 after the intravitreal Ozurdex. No further recurrences of exudation were evident through the 12-month follow-up. CONCLUSIONS: Ozurdex may be an effective initial therapeutic approach for Coats' disease with immediate anatomical response and visual improvement.

Celecoxib for recurrent sclerouveitis after syphilitic panuveitis. A case report.

PURPOSE: To report a case of recurrent ocular inflammation after optimal therapy of bilateral syphilitic panuveitis responding to oral celecoxib. METHODS: A case report was conducted. RESULTS: A 76-year-old man presented with painful blurry vision in both eyes. Ocular examination disclosed bilateral panuveitis. Serological testing confirmed blood and cerebrospinal fluid syphilitic involvement. After 2 weeks of intravenous penicillin therapy, recurrent episodic sclerouveitis was observed. CONCLUSION: Ocular inflammation after healing of infectious uveitis is a rare ophthalmic sequela. In an immunocompetent patient, either re-infection or immune uveitis should be evoked. Non-steroidal therapeutic options, as celecoxib, could be a good option of treatment in such immune cases.