The Glaucoma Italian Pediatric Study (GIPSy): The Long-term Effect of Topical Latanoprost on Central Corneal Thickness.

PRECIS: Central corneal thickness (CCT) may increase over time in children affected by primary congenital glaucoma and treated with latanoprost for at least 30 months. PURPOSE: The purpose of this study was to investigate CCT modification over time in a population of primary pediatric glaucoma (PPG) patients prescribed a monotherapy of latanoprost. MATERIALS AND METHODS: The present paper reports the results of a post hoc analysis on patients enrolled in the Glaucoma Italian Pediatric Study (GIPSy). Children affected by PPG, with a postsurgical intraocular pressure between 22 and 26 mm Hg and treated with latanoprost monotherapy for at least 30 months were eligible for the analysis. CCT variation from baseline was investigated over the follow-up using univariable and multivariable longitudinal linear mixed models. The impact of age, sex, and intraocular pressure on CCT variation were evaluated taking into account the interaction of each variable with time. RESULTS: Twenty-seven eyes (20 patients) were included in the analysis. Mean duration of latanoprost treatment was 36.6 months (SD 2.5) and mean CCT at baseline was 551 µm (SD 37.7). A significant increase of CCT over time was revealed by multivariable analysis, taking into account the impact of age at baseline and its interaction with time (P=0.03). The interaction between age and time was significant (P=0.04), indicating that older age at baseline was associated with lower increase of CCT over time. No variation of CCT was found in univariable analysis (P=0.28). CONCLUSION: In this population of PPG patients treated with latanoprost for at least 30 months, CCT significantly increased over time, when the impact of age and its interaction with time were considered.

How many aqueous humor outflow pathways are there?

The aqueous humor (AH) outflow pathways definition is still matter of intense debate. To date, the differentiation between conventional (trabecular meshwork) and unconventional (uveoscleral) pathways is widely accepted, distinguishing the different impact of the intraocular pressure on the AH outflow rate. Although the conventional route is recognized to host the main sites for intraocular pressure regulation, the unconventional pathway, with its great potential for AH resorption, seems to act as a sort of relief valve, especially when the trabecular resistance rises. Recent evidence demonstrates the presence of lymphatic channels in the eye and proposes that they may participate in the overall AH drainage and intraocular pressure regulation, in a presumably adaptive fashion. For this reason, the uveolymphatic route is increasingly thought to play an important role in the ocular hydrodynamic system physiology. As a result of the unconventional pathway characteristics, hydrodynamic disorders do not develop until the adaptive routes cannot successfully counterbalance the increased AH outflow resistance. When their adaptive mechanisms fail, glaucoma occurs. Our review deals with the standard and newly discovered AH outflow routes, with particular attention to the importance they may have in opening new therapeutic strategies in the treatment of ocular hypertension and glaucoma.

The Glaucoma Italian Pediatric Study (GIPSy): 3-Year Results.

PURPOSE: To investigate the efficacy and safety of a treatment strategy with latanoprost and dorzolamide in primary pediatric glaucoma patients partially responsive to surgery. PATIENTS AND METHODS: Children with primary pediatric glaucoma with postsurgical intraocular pressure (IOP) between 22 and 26 mm Hg were eligible. At baseline, patients were administered latanoprost once daily. Depending on IOP reduction, patients were allocated to continuation of latanoprost monotherapy or addition of dorzolamide twice daily, or switch to dorzolamide monotherapy 3 times daily. Patients in the dorzolamide monotherapy group with IOP reduction <20% from baseline were considered nonresponders. The primary endpoint was the percentage of responders. Study treatment continued for 3 years or until treatment failure. RESULTS: A total of 37 patients (61 eyes) were analyzed. The mean age of the patients was 4.1 years (SD: 3.8). In total, 43 eyes were included in the efficacy analysis. A total of 33 eyes (76.7%; 95% confidence interval, 61.4-88.2) were considered responders: 19 on latanoprost monotherapy, 11 on the latanoprost/dorzolamide combination, and only 3 on the dorzolamide monotherapy. The efficacy of pharmacological treatment was inversely related to central corneal thickness at the time of surgery and the age at the time of surgery. IOP reduction was 9.7 mm Hg (SD: 2.6) for latanoprost, 8.4 mm Hg (SD: 1.5) for the latanoprost/dorzolamide combination, and 9.3 mm Hg (SD: 2.5) for the dorzolamide monotherapy. None of the patients was withdrawn because of adverse events. CONCLUSIONS: Latanoprost alone or in combination with dorzolamide is safe and highly effective in lowering IOP in children after surgery. Nonresponders were mainly patients with early presentation of the disease.

Morphology of the optic nerve head in glaucomatous eyes with visual field defects in superior or inferior hemifield.

PURPOSE: To evaluate the morphology of optic nerve head (ONH) and border tissue (BT) of Elschnig in glaucomatous eyes with visual field defects in superior or inferior hemifield. METHODS: In a case-control study, we included 25 patients with superior arcuate scotoma, 25 patients with inferior arcuate scotoma, and 25 healthy controls. They received visual field testing, measurement of peripapillary retinal nerve fiber layer (RNFL) thickness, and ONH examination in a radial pattern with spectral-domain optical coherence tomography. In each ONH scan, the length of Bruch membrane opening (BMO) and BT were measured. Pattern deviation of 6 areas of the visual field and RNFL thickness in corresponding sectors was calculated. RESULTS: Mean BMO length did not differ between groups. Compared with controls, glaucomatous eyes with superior scotoma had a greater BT length in inferior sectors (p<0.001), and eyes with inferior scotoma had a greater BT length in superotemporal sectors (p = 0.006). In both groups, a significant correlation was found between BT length and pattern deviation and RNFL thickness of corresponding sectors of superior and inferior hemifields. CONCLUSIONS: In patients with arcuate scotoma in one hemifield, the length of the BT correlates with glaucomatous anatomical and functional damage.

DEXAMETHASONE INTRAVITREAL IMPLANT VS RANIBIZUMAB IN THE TREATMENT OF MACULAR EDEMA SECONDARY TO BRACHYTHERAPY FOR CHOROIDAL MELANOMA.

PURPOSE: To evaluate the efficacy of an intravitreal dexamethasone (Dex) implant 0.7 mg compared with intravitreal ranibizumab (Ra) for the treatment of radiation maculopathy with macular edema secondary to plaque brachytherapy in choroidal melanoma. METHODS: Eight patients were treated with intravitreal Ra, and eight patients received the Dex intravitreal implant. Visual acuity and foveal thickness were evaluated using spectral domain optical coherence tomography. RESULTS: The mean calculated irradiation to the fovea and mean times from brachytherapy to maculopathy development did not differ significantly between groups. In the Ra group, a mean 7.8 ± 3.9 injections were given and the mean follow-up was 33 ± 15 months (range, 7-52 months). In the Dex group, a mean 2.1 ± 0.8 injections were given and the mean follow-up was 22 ± 7 months (range, 11-31 months). The mean visual acuity improved significantly from the baseline to the last follow-up visit in both groups. Foveal thickness decreased significantly in both groups from 459 ± 81 µm to 243 ± 58 µm and from 437 ± 71 µm to 254 ± 44 µm from the baseline to the last follow-up visit in the Ra and Dex groups, respectively. No patients developed significant cataract or ocular hypertension in both groups. CONCLUSION: Both Ra and Dex are effective treatments for macular edema secondary to plaque brachytherapy for uveal melanoma. Dex-treated patients required fewer injections to achieve anatomical and functional improvement.

The Glaucoma Italian Pediatric Study (GIPSy): 1-Year Results.

PURPOSE: To investigate the efficacy and safety of a treatment strategy with latanoprost and dorzolamide in primary pediatric glaucoma patients partially responsive to surgery. PATIENTS AND METHODS: Children with primary pediatric glaucoma having postsurgical untreated intraocular pressure (IOP) between 22 and 26 mm Hg were eligible. At baseline, patients were administered latanoprost once daily. Depending on IOP reduction, patients were allocated to continuation of latanoprost monotherapy or addition of dorzolamide twice daily, or switch to dorzolamide monotherapy 3 times daily. Patients in the dorzolamide monotherapy group with IOP reduction <20% from baseline were considered nonresponders. The primary endpoint was the percentage of responders. Study treatment continued for 3 years or until treatment failure. The present article reports the 1-year analysis results. RESULTS: A total of 35 patients (57 eyes) were analyzed. The mean age was 4.0 years (SD, 3.8). In total, 51 eyes were included in the efficacy analysis. In total, 43 eyes (84.3%; 95% confidence interval, 74.3-94.3) were considered responders: 29 on latanoprost monotherapy, 11 on the latanoprost/dorzolamide combination, and only 3 on the dorzolamide monotherapy. The efficacy of pharmacological treatment was inversely related to the age at the time of surgery. IOP reduction was 8.7 mm Hg (SD, 2.2) for latanoprost, 7.5 mm Hg (SD, 1.4) for the latanoprost/dorzolamide combination, and 8.7 mm Hg (SD, 2.1) for the dorzolamide monotherapy. Only mild or moderate local adverse events were noted. None of the patients was withdrawn due to adverse events. CONCLUSION: Latanoprost alone or in combination with dorzolamide is safe and highly effective in lowering IOP in children postsurgery. Nonresponders were mainly patients with early presentation of the disease.

Correction: miRNAs in the vitreous humor of patients affected by idiopathic epiretinal membrane and macular hole.

[This corrects the article DOI: 10.1371/journal.pone.0174297.].

Optic nerve head in central retinal vein occlusion by spectral-domain OCT.

PURPOSE: To evaluate the morphology of optic nerve head by spectral-domain optical coherence tomography (SD-OCT) in patients with unilateral central retinal vein occlusion (CRVO). METHODS: In 39 consecutive patients with unilateral CRVO and 39 healthy controls, morphologic parameters of optic nerve head were assessed in both eyes by Spectralis SD-OCT using a custom radial B-scan pattern. The length of Bruch membrane opening (BMO) was measured in OCT scans, and optic disc diameters (DD) were assessed in infrared fundus photographs. Axial length was determined by IOLMaster. RESULTS: The BMO length was measured in all eyes with CRVO, while DD was not assessed in 9 eyes (27.3%) that had undefined disc margins. Compared to healthy controls (mean BMO length 1,511 ± 79 µm, mean disc diameter 1,521 ± 77 µm), in eyes with CRVO with defined disc margins (n = 28 [71.8%]), no significant difference was found in BMO length and DD (1,473 ± 118 µm and 1,516 ± 104 µm, respectively). Eyes with CRVO with undefined disc margins had lower BMO length (1,289 ± 61 µm [-14.7%], p = 0.001); also, in fellow eyes, these patients had lower BMO length and DD. In all groups, no significant difference was seen between BMO and DD. A correlation was found between axial length and BMO length and disc diameter (both p<0.001). CONCLUSIONS: Most of the eyes with CRVO had normal optic disc diameter, but about 25% of patients with CRVO have reduced optic disc dimensions.

miRNAs in the vitreous humor of patients affected by idiopathic epiretinal membrane and macular hole.

PURPOSE: The aim of the present study was to assess the expression of miRNAs in the Vitreous Humor (VH) of patients with Macular Hole (MH) and Epiretinal Membrane (ERM) compared to a control group. METHODS: In this prospective, comparative study, 2-ml of VH was extracted from the core of the vitreous chamber in consecutive patients who underwent standard vitrectomy for ERM and MH. RNA was extracted and TaqMan® Low Density Arrays (TLDAs) were used to profile the transcriptome of 754 miRNAs. Results were validated by single TaqMan® assays. Finally, we created a biological network of differentially expressed miRNA targets and their nearest neighbors. RESULTS: Overall 10 eyes with MH, 16 eyes with idiopathic ERM and 6 controls were enrolled in the study. Profiling data identified 5 miRNAs differentially expressed in patients affected by MH and ERM with respect to controls. Four were downregulated (miR-19b, miR-24, miR-155, miR-451) and 1 was downregulated (miR-29a); TaqMan® assays of the VH of patients affected by MH and ERM, with respect to controls, showed that the most differentially expressed were miR-19b (FC -9.13, p:<0.00004), mir-24 (FC -7.52, p:<0.004) and miR-142-3p (FC -5.32, p:<0.011). Our network data showed that deregulation of differentially expressed miRNAs induces an alteration of several pathways associated with genes involved in both MH and ERM. CONCLUSION: The present study suggests that disregulation of miR-19b, miR-24 and miR-142-3p, might be related to the alterations that characterize patients affected by MH and ERM.

Association of neovascular age-related macular degeneration with month and season of birth in Italy.

In order to investigate the influence of season and month of birth on the risk of neovascular age-related macular degeneration (n-AMD) in Italy, we evaluated the month birth and sex of all patients, recorded in the anti-vascular endothelial growth factor (VEGF) monitoring registry of the Italian Medicines Agency, born between 1925-1944, who received intravitreal anti-VEGF injections for n-AMD between January 1, 2013 and July 29, 2015. The numbers of all births in Italy in the same years, extracted from the Italian National Institute of Statistics, were used to calculate the expected number of n-AMD cases. Overall, 45,845 patients (19,207 men, 26,638 women) received intravitreal anti-VEGF for n-AMD; in the same years, 20,140,426 people (10,334,262 male, 9,806,164 female) were born in Italy. Comparing the observed number of n-AMD cases with the expected number of n- AMD cases in each season, we found that the season-specific risk for n-AMD was 2.5% higher for those born in summer (OR=1.03, Bonferroni-corrected P=0.008) and 3% lower for those born in winter (OR=0.96, Bonferroni-corrected P=0.0004). When considering the month of birth, the risk of n-AMD was 5.9% lower for people born in January (OR=0.93, Bonferroni-corrected P=0.0012). The factors causing such differences should be determined.

Latanoprost and Dorzolamide for the Treatment of Pediatric Glaucoma: The Glaucoma Italian Pediatric Study (Gipsy), Design and Baseline Characteristics.

INTRODUCTION: To investigate the efficacy of a treatment strategy with latanoprost and dorzolamide in primary pediatric glaucoma patients partially responsive to surgery. METHODS: Single arm, prospective, interventional multicenter study. Primary pediatric glaucoma patients younger than 13 years after a single surgical procedure with IOP between 22 and 26 mmHg were considered eligible. At baseline, patients were allocated to latanoprost monotherapy once daily. Depending on intraocular pressure (IOP) reduction at first visit, the patients were allocated to one of three groups: continuation of latanoprost monotherapy, addition of dorzolamide twice daily, or switch to dorzolamide three times daily. The same approach for allocation in medication groups was used in all subsequent visits. Patients in the dorzolamide monotherapy group with IOP reduction <20% from baseline were considered non-responders and withdrawn. Study treatment and patient follow-up will continue for 3 years or until treatment failure. The primary endpoint is the percentage of responders. Secondary endpoints are time to treatment failure and frequency of adverse events. RESULTS: A total of 37 patients (69 eyes) were enrolled. The mean age was 4.0 ± 3.8 years, the female/male ratio was 1/1.7, and the majority of patients were Caucasian. Eighty percent of patients had bilateral glaucoma. Goniotomy was the most frequently performed surgery (38.6%), followed by trabeculotomy (22.8%), trabeculectomy (21.1%), and trabeculectomy plus trabeculotomy (17.5%). The baseline IOP was 23.6 ± 1.5 mmHg. CONCLUSION: The study population is representative of patients frequently encountered after the first surgery for primary pediatric glaucoma. The study will produce evidence on the medium-term efficacy of a defined pharmacological approach.

Acute serous macular detachment and edema after uncomplicated phacoemulsification: A case series.

OBJECTIVE: To report cases of acute serous macular detachment and edema after uncomplicated phacoemulsification. DESIGN: Retrospective case series. PARTICIPANTS: We reviewed the clinical data of 5 patients who developed an acute serous macular detachment and edema after uncomplicated phacoemulsification with intraocular lens implantation by the same expert surgeon and without any complication during surgery. METHODS: Best corrected visual acuity (BCVA), biomicroscopy, fundus examination, and optical coherence tomography were performed at 1, 3, 7, and 30 postoperative days. RESULTS: On the first postoperative day, all eyes had low visual acuity (median 1.0 logMAR) despite normal postoperative appearance of the anterior segment. Optical coherence tomography showed serous macular detachment with intraretinal fluid accumulation. After treatment with oral indomethacin and acetazolamide, at 7 days, intraretinal and subretinal fluid were fully reabsorbed and BCVA improved (at least 0.1 logMAR). In the following 6 months, no eye had recurrence of macular edema. CONCLUSIONS: Acute serous macular detachment and edema can occur after uncomplicated phacoemulsification. It should be considered in cases of low visual acuity during the early postoperative period.

Effects of Topical Fucosyl-Lactose, a Milk Oligosaccharide, on Dry Eye Model: An Example of Nutraceutical Candidate.

PURPOSE: Colostrum has been proposed to treat severe dryness and problematic eye lesions showing a beneficial effect. The aim of the study was to investigate the effect of 2-fucosyl-lactose, a natural sugar present in the human colostrum, in an experimental dry eye. METHODS: Dry eye was induced in adult male New Zealand albino rabbits by topical administration of 1% atropine. Tear volume (Schirmer's test), tear film breakup time (TBUT), corneal staining and tear osmolarity were assessed. Fucosyl-lactose eye drops was instilled at different concentrations (0.01, 0.1, and, 1%). RESULTS: After 24 h from first atropine administration, tear volume and TBUT values were significantly improved in groups treated with 2-fucosyl-lactose in a dose-dependent manner. Tear volume increased from 5.25 to 10.75 mm and TBUT values from 8.75 to 34.5 s with 0.01% or 1% 2-fucosyl-lactose treatment, respectively. No changes were observed in terms of corneal staining among the all groups treated with 2-fucosyl-lactose. Atropine instillation caused an increase of tear osmolarity (428 mOsm/L), which was reversed by topical treatment with 2-fucosyl-lactose at all doses. CONCLUSION: The present study demonstrated that 2-fucosyl-lactose, a human milk oligosaccharide, has protective effect on tear film stability.

Intravitreal Steroids for the Prevention of PVR After Surgery for Retinal Detachment.

Proliferative vitreoretinopathy (PVR) can occur in eyes with rhegmatogenous retinal detachment (RRD) or after RRD surgery, and it is the most common cause of failure of this surgery, accounting for about 75% of all primary failures. Complex biological pathways induce PVR development, with growth factors and cytokines from the vitreous and from the serum (as a result of the breakdown of the blood-retinal barrier) stimulating RPE and Muller cells transformation and proliferation, and membrane formation and contraction. Identification of pre-operative risk factors, recognition of the early signs of PVR, use of adequate surgical techniques and of pharmacological therapy can reduce the PRV incidence. Steroids can influence the inflammatory and proliferative components of PVR, by reducing the breakdown of the blood-retinal barrier, and the proliferation of Müller cell and of RPE cells. Some new formulation of intravitreal steroids are promising tool for the prevention of the PVR formation in eyes treated by vitreoretinal surgery.

Intravitreal dexamethasone implant for cystoid macular edema and inflammation after scleral buckling.

PURPOSE: Cystoid macular edema may occur following scleral buckling and therefore deteriorate the visual outcome. Inflammation may be the major causative factor in the development of postoperative cystoid macular edema. This case demonstrates the effectiveness of a dexamethasone implant as a treatment after the onset of choroidal inflammation and cystoid macular edema 6 months following scleral buckling and having visual acuity restored. METHODS: A 59-year-old phakic woman treated with scleral buckling for macula-off retinal detachment presented 2 months after surgery with cystoid macular edema with choroidal inflammation. Optical coherence tomography and fluorescein angiography were performed. From the time of the diagnosis, the patient's condition had been nonresponsive to medical therapy and only partially responsive to sub-Tenon triamcinolone acetonide. An intravitreal implant with a sustained release of 0.7 mg dexamethasone was implanted. RESULTS: Following an intravitreal injection with a dexamethasone implant, the macular edema subsided completely and optical coherence tomography showed decreased foveal thickness from 510 µm to 220 µm. Choroidal fluorescein leakage disappeared. Best-corrected visual acuity improved from 0.70 to 0.20 logMAR, a condition maintained throughout the 6 months of follow-up. CONCLUSIONS: Cystoid macular edema and choroidal inflammation are difficult to treat, but the improvement observed in this case of post scleral buckling macular edema and choroidal inflammation showed how a dexamethasone implant proved to be useful during the 6-month follow-up.

Cellular stress response, redox status, and vitagenes in glaucoma: a systemic oxidant disorder linked to Alzheimer's disease.

Amyloid deposits, constituted of amyloid beta (Aß) aggregates, are a characteristic feature of several neurodegenerative diseases, such as Alzheimer's, mild cognitive impairment and Parkinson's disease. They also have been recently implicated in the pathogenesis of retinal damage, as well as age-related macular degeneration and glaucoma. Glaucoma is a progressive optic neuropathy characterized by gradual degeneration of neuronal tissue due to retinal ganglion cell loss, associated to visual field loss over time resulting in irreversible blindness. Accumulation of Aß characterizes glaucoma as a protein misfolding disease, suggesting a pathogenic role for oxidative stress in the pathogenesis of retinal degenerative damage associated to glaucoma. There is a growing body of evidence demonstrating a link between Alzheimer's disease and glaucoma. Further, several heat shock proteins (HSPs) members have been implicated both in neurodegenerative diseases and glaucomatous apoptosis. To maintain redox homeostasis vitagenes, as integrated mechanisms, operate actively to preserve cell survival under condition of stress. Vitagenes encode for sirtuin, thioredoxin and HSPs. The present study was designed to investigate cellular stress response mechanisms in the blood of patients with glaucoma, compared to control subjects. Levels of vitagenes HSP-72, heme oxygenase-1, as well as F2-isoprostanes were significantly higher in the blood of patients with glaucoma than in controls. Furthermore, in the same experimental group increased expression of Trx and sirtuin 1 were measured. Our results sustain the importance of redox homeostasis disruption in the pathogenesis of glaucoma and highlights the opportunity that new therapies that prevents neurodegeneration through non-immunomodulatory mechanisms might be synergistically associated with current glaucoma therapies, thus unraveling important targets for novel cytoprotective strategies.

Treatment of persistent serous retinal detachment in Vogt-Koyanagi-Harada syndrome with intravitreal bevacizumab during the systemic steroid treatment.

PURPOSE: To report the use of bevacizumab in patients with Vogt-Koyanagi-Harada disease and persistent serous retinal detachment during the systemic steroid treatment. METHODS: Four patients with bilateral Vogt-Koyanagi-Harada disease with the resolution of ocular inflammation presenting a serous retinal detachment involving the fovea that persisted for at least 1 month, despite systemic corticosteroid treatment, received an intravitreal injection of bevacizumab during the steroid tapering stage. Best-corrected visual acuity, central retinal thickness, and macular sensitivity were evaluated. RESULTS: Of 8 eyes, 7 (87%) had complete resolution of subretinal fluid within 1 month following the treatment. After the treatment, the mean best-corrected visual acuity and macular sensitivity improved significantly (P < 0.001, analysis of variance). Compared with baseline, at all measurements, central retinal thickness decreased significantly (P < 0.01, Tukey-Kramer test). At 6 months, a significant correlation was found between best-corrected visual acuity and macular sensitivity in the central 8° (linear regression, r = -0.73; P = 0.03), whereas no correlation was found between central retinal thickness and both best-corrected visual acuity and macular sensitivity. CONCLUSION: Intravitreal injection of bevacizumab during the corticosteroid therapy may be a treatment option for patients with decreased visual function because of persistent serous retinal detachment associated with Vogt-Koyanagi-Harada syndrome.

Rhegmatogenous Retinal Detachment with a High Risk of Proliferative Vitreoretinopathy Treated with Episcleral Surgery and an Intravitreal Dexamethasone 0.7-mg Implant.

PURPOSE: To report a case of rhegmatogenous retinal detachment with a high risk of proliferative vitreoretinopathy (PVR) effectively treated with episcleral surgery and an intravitreal dexamethasone 0.7-mg implant. METHODS: A 35-year-old Caucasian man with a macula-off rhegmatogenous subtotal retinal detachment that had persisted for 1 month in his myopic left eye presented several risk factors that could have led to the development of PVR after retinal detachment surgery. His best corrected visual acuity was hand motion. He received an intravitreal dexamethasone 0.7-mg implant (Ozurdex(®)) after episcleral surgery to prevent this complication. RESULTS: At least 9 months after surgery, no sign of PVR or pucker has developed in the treated eye. Visual acuity improved to 0.2, the retina was attached and no complications were observed. CONCLUSION: Intravitreal dexamethasone 0.7-mg implant (Ozurdex) could be considered as off-label treatment following episcleral surgery to prevent PVR.

Pattern ERG and RNFL thickness in hypertensive eyes with normal blue-yellow visual field.

PURPOSE: To evaluate the transient pattern electroretinogram (t-PERG) and the retinal nerve fiber layer (RNFL) thickness in eyes with ocular hypertension (OH) and normal short-wavelength automated perimetry (SWAP). METHODS: In 26 patients with bilateral OH with normal SWAP, and in 26 age and sex matched healthy controls, t-PERG recording and RNFL thickness measurement were performed. Mean deviation (MD) and pattern standard deviation (PSD) of a reliable full threshold 24-2 SWAP were considered. RNFL thickness was determined by OCT3. Monocular PERG were recorded by using a black and white checkerboard pattern (check size 0.9°, contrast 100 %, mean luminance 80 cd/m2) generated on a monitor and reversed in contrast (four reversals per second, 2 Hz) at a distance of 70 cm. Patients had optimal correction at viewing distance; no mydriatic or miotic eye drops were used. Silver/silver chloride skin electrodes were placed over the lower eyelids in the stimulated eye (active electrode) and in the patched eye (reference electrode); ground electrode was in the Fpz scalp. Peak-to peak amplitude of P50 (N35-P50) and N95 (P50-N95) waves, and implicit time of P50, were considered. RESULTS: Compared to controls, in OH eyes, a reduction of N35-P50 amplitude (2.86 ± 1.49 vs. 3.77 ± 1.08 microvolts, -24.1 %, t-test p = 0.015), of average RNFL thickness (88 ± 11 vs. 96 ± 10 µm, -9.5 %, t-test p = 0.002), and of RNFL thickness in superior (p = 0.015) and inferior quadrant (p < 0.001), were found. Multivariate analysis showed that in OH eyes, N35-P50 amplitude was inversely related to intraocular pressure (IOP) (p = 0.001); no correlation was found between N35-P50 amplitude and MD, PSD, CCT or RNFL thickness. CONCLUSIONS: In OH eyes, both PERG and RNFL thickness changes occur in hypertensive eyes with undamaged SWAP; the correlation of PERG amplitude with IOP, but not with RNFL thickness, suggests that such PERG changes are an effect of the IOP on retinal ganglion cells, rather than a sign of their loss.

Oral administration of forskolin and rutin contributes to intraocular pressure control in primary open angle glaucoma patients under maximum tolerated medical therapy.

BACKGROUND: Tight control of intraocular pressure (IOP) is still the only therapeutic approach available for the treatment of primary open angle glaucoma (POAG). However, some patients do not respond adequately to hypotonising drugs, and despite multiple drug combinations they cannot reach their target IOP. Forskolin is a natural compound that has already shown efficacy in IOP reduction following topical application. PURPOSE: The aim of this study was to evaluate the effects on the IOP of a food supplement containing forskolin and rutin when administered to POAG patients under maximum tolerated medical therapy (MTMT) and on a waiting list for filtrating surgery to further decrease their IOP. METHODS: The design of the study was open and case-controlled. Ninety-seven (52 in the treatment group, and 45 in the reference group) patients were enrolled in 8 different glaucoma centers in Italy, all under MTMT and with IOP enrollment values above their target pressure. During the 30 days before surgery, patients in the treatment group were prescribed 2 tablets per day of a food supplement containing rutin and forskolin in addition to their usual topical drug treatment. Their IOP values were measured at 3 time points during the day, at enrollment and once a week until surgery. Control patients continued only with their normal topical therapy. RESULTS: All patients in the treatment group, independently of the combination drug therapy that they were taking, showed a further 10% decrease (P<0.01) of their IOP, starting from 1 week after introduction of the oral supplement and lasting until the last evaluation before surgery. This decrease was more evident (15% of the enrollment value; P<0.01) in those subjects with high (IOP≥21 mmHg) enrollment values rather than in those with low (IOP<21) enrollment values (9%; P<0.01). On the contrary, IOP values in the control group remained stable from the beginning to the end of the observation period, independently of their enrollment values. CONCLUSIONS: Forskolin and rutin given as oral treatment appear to contribute to a better control and a further small reduction of IOP in patients who were poorly responsive to multitherapy treatment.