Treatment of Capecitabine Corneal Side Effects With Autologous Blood-derived Serum Eye Drops.

BACKGROUND/AIM: To describe the clinical progress and management of ocular side effects in a 35-year-old patient with metastatic breast cancer who underwent oral chemotherapy with capecitabine and lapatinib. MATERIALS AND METHODS: Slit lamp evaluation revealed bilateral perikeratic hyperemia, perilimbal conjunctival edema associated with corneal marginal infiltrates and epithelial and anterior stromal defects in both eyes. Slit lamp examination, in vivo confocal microscopy and anterior-segment optical coherence tomography were highly suggestive for limbal stem cell deficiency. The decision to administer autologous blood- derived serum eye drops was made. RESULTS: Following administration of autologous blood-derived serum eye drops, corneal marginal infiltrates, epithelial and stromal defects significantly regressed in both eyes after only 10 days. Chemotherapy was resumed and serum eye drops were prescribed simultaneously. CONCLUSION: Autologous blood-derived serum eye drops may be an adequate therapeutic choice for bilateral corneal lesions detected as ocular side effects of capecitabine.

Anatomical and functional changes after dexamethasone implant and ranibizumab in diabetic macular edema: a retrospective cohort study.

AIM: To investigate the efficacy and safety of ranibizumab (RZB group) and dexamethasone implant (DEX group) intravitreal treatments in patients with treatment-naïve center involved diabetic macular edema (DME) by means of functional and morphological assessments. METHODS: This retrospective cohort study included 50 eyes of 50 patients with DME treated either with RBZ or DEX. Best-corrected visual acuity (BCVA) and microperimetry were evaluated at baseline and during a 6-month follow-up. In addition, central macular thickness (CMT) by means of structural optical coherence tomography (OCT) and retinal capillary plexus density and choriocapillary density by means of OCT angiography were assessed in all cases. RESULTS: Functional and morphological parameters significantly improved during the study period in both groups. BCVA improved significantly in both groups with a greater increase in the DEX group compared to the RBZ group (P=0.030). Microperimetry significantly differed during follow-up between the two treatments (P=0.031). In both groups CMT significantly decreased (P<0.001) without statistically significant differences between the two groups. A statistically significant increase of deep capillary plexus density was detected in both groups at 30d after therapy. The retreatment rate was 0.70±0.10 and 0.65±0.10 in the RBZ group and 0.65±0.10 and 0.50±0.11 in DEX group at 120 and 180d respectively. Two out of 25 patients in DEX group showed intraocular pressure increase requiring hypotonic eye drops. CONCLUSION: Both treatments are very effective for DME treatment during 6mo of follow-up with a lower retreatment rate in DEX group.

The retinoprotective role of phenytoin.

Phenytoin is a non-sedative barbiturate derivate and has been recently rediscovered as a neuroprotective and retinoprotective compound in patients affected by optic neuritis secondary to multiple sclerosis. However, currently there are still no neuroprotective compounds registered and available in the clinic. We reviewed the literature supporting the retinoprotective properties of phenytoin and analyzed the various approaches and definitions from the first research periods onwards. The retinoprotective role of phenytoin was already known in the 1970s, but only recently has this effect been rediscovered, confirming that it could indeed provide structural protection of the retinal cells.

Analysis of differences in intraocular pressure evaluation performed with contact and non-contact devices.

BACKGROUND: To evaluate differences of intraocular pressure (IOP) measurements performed with Goldmann applanation tonometer (GAT), dynamic contour tonometer (DCT), rebound tonometry (RT), Ocular Response Analyzer (ORA) and Corvis ST (CST) in eyes screened for refractive surgery. METHODS: One eye, only the right one, of 146 patients was included in this study. Each participant was submitted to a corneal analysis with Scheimpflug camera and IOP evaluation with GAT, DCT, RT, ORA and CST. Differences in IOP values obtained thanks to each instruments were compared and then correlations between these discrepancies and morphological features such as mean keratometry (MK) and central corneal thickness (CCT) provided by Pentacam were studied. Software used to run statistical evaluations was SPSS, version 18.0. RESULTS: Study participants had a mean age of 33.1 ± 9.2 years old. IOP values observed in this study were 15.97 ± 2.47 mmHg (GAT), 17.55 ± 2.42 mmHg (DCT), 17.49 ± 2.08 mmHg (RT), 18.51 ± 2.59 mmHg (ORA) and 18.33 ± 2.31 mmHg (CST). The mean CCT was 560.23 ± 31.00 µm, and the mean MK was 43.33 ± 1.35 D. GAT provided significant lower values in comparison to all other devices. DCT and RT gave significantly lower intermediate IOP values than those measured with ORA and CST. All the IOP measures and the differences between devices were significantly correlated with CCT. CONCLUSIONS: According to our data, although our findings should be confirmed in further studies, GAT tonometer cannot be used interchangeably with DCT, RT, ORA and CST.

Diagnostic capability of optic nerve head rim width and retinal nerve fiber thickness in open-angle glaucoma.

PURPOSE: This study was performed to test the diagnostic capability of the minimum rim width compared to peripapillary retinal nerve fiber layer thickness in patients with glaucoma. METHODS: A case control, observer masked study, was conducted. Minimum rim width and retinal nerve fiber layer thickness were assessed using the patient-specific axis traced between fovea-to-Bruch's membrane opening center axis. For both minimum rim width and retinal nerve fiber layer thickness, the regionalization in six sectors (nasal, superior-nasal, superior-temporal, temporal, inferior-temporal, and inferior-nasal) was analyzed. Eyes with at least one sector with value below the 5% or 1% normative limit of the optical coherence tomography normative database were classified as glaucomatous. The area under the receiver operator characteristic curve, the accuracy, sensitivity, specificity, and predictive positive and negative values were calculated for both minimum rim width and retinal nerve fiber layer thickness. RESULTS: A total of 118 eyes of 118 Caucasian subjects (80 eyes with open-angle glaucoma and 38 control eyes) were enrolled in the study. Accuracy, sensitivity, and specificity were 79.7%, 77.5%, and 84.2%, respectively, for minimum rim width and 84.7%, 82.5%, and 89.5% for retinal nerve fiber layer thickness. The positive predictive values were 0.91% and 0.94% for minimum rim width and retinal nerve fiber layer thickness, respectively, whereas the negative predictive values were 0.64% and 0.70%. The area under the receiver operator characteristic curve was 0.892 for minimum rim width and 0.938 for retinal nerve fiber layer thickness. CONCLUSION: Our results indicated that the sector analysis based on Bruch's membrane opening and fovea to disk alignment is able to detect glaucomatous defects, and that Bruch's membrane opening minimum rim width and retinal nerve fiber layer thickness showed equivalent diagnostic ability.

In Vivo Analysis of Prostaglandins-induced Ocular Surface and Periocular Adnexa Modifications in Patients with Glaucoma.

BACKGROUND/AIM: Prostaglandin analogues (PGAs) are a first-line medical treatment for glaucoma because of their powerful intraocular pressure (IOP) lowering effect, few systemic side-effects (SEs), and the once daily administration. Despite the high systemic safety profile, the chronic use of PGAs may induce periocular and ocular surface (OS)-related side effects, which affect a significant proportion of glaucomatous patients. In this review, we summarize the current knowledge about SEs of PGAs on periocular structures and OS, and their implications in clinical practice. MATERIALS AND METHODS: A comprehensive literature search on the PubMed platform was performed. Two hundred fifty articles fulfilling key words were identified, of which 180 were excluded since they did not concern the effects of PGAs on the periocular tissues and OS, or because of their limited relevance. The following key words were used and combined, to narrow-down the literature: "prostaglandin" and "ocular surface," which identified 184 unique publications, of which 68 were selected; "prostaglandin" and "periocular" which identified 46 unique publications, of which 11 were selected. An additional search was conducted using "prostaglandin" and "Meibomian glands (MGs)", which identified twenty unique publications, of which 8 were selected. Thus, a total of 70 articles were chosen based on their relevance and were included in this review. RESULTS: Prostaglandin-associated peri-orbitopathy, skin pigmentation and hypertrichosis, eyelash growth, and MGs dysfunction are the most frequent modifications of periocular tissues. They are induced by the tissue accumulation of PGAs, and FP receptor stimulation. Without preservatives, PGAs act as stimulators of conjunctival goblet cells, which are the main source of ocular surface mucoproteins, and seem to increase conjunctival epithelium microcysts proposed as in vivo hallmark of the trans-scleral aqueous humour outflow. Additional PGA-induced modifications can be recognized in the cornea, corneo-scleral limbus, conjunctival stroma and, conjunctiva-associated lymphoid tissue, mainly appearing as inflammatory changes. OS epithelia desquamation, chemosis, apoptosis, dendritic cell activation, conjunctival or episcleral vasodilation, and sub-basal nerve plexus disruption were also described in patients receiving preserved PGAs. CONCLUSION: PGAs induce several modifications of the OS structures and adnexa; nonetheless, none of them significantly reduces the local safety profile of this class of drugs. Moreover, the OS changes do not affect the IOP lowering efficacy of PGAs. On these bases, local SEs of PGAs should not discourage clinicians in using this class of medications because of their efficacy, the systemic safety profile, and the better adherence.

In Vivo Scanning Laser Confocal Microscopy of Conjunctival Goblet Cells in Medically-controlled Glaucoma.

AIM: The aim of this study was to evaluate the goblet cell density (GCD) of conjunctiva in medically-controlled glaucoma using laser scanning confocal microscopy (LSCM). MATERIALS AND METHODS: Fifty-five glaucomatous patients were enrolled and divided into two groups: Group 1 (27 eyes), controlled with one medication; and group 2 (28 eyes), controlled with two medications. Seventeen patients with dry eye disease (DED) and 17 healthy individuals served as controls. Patients completed the Ocular Surface Disease Index (OSDI) questionnaire and underwent determination of tear film break-up time (BUT), corneal staining, and Schirmer test I. For the GCD assessment, 12 high-quality images were acquired from the upper conjunctival epithelium (superior nasal, superior central, and superior temporal sectors). RESULTS: Overall, GCD was significantly reduced in both glaucoma groups and those with DED compared to healthy controls (p<0.001), with values markedly lower in group 2 compared to group 1 (p<0.05). GCD was not significantly different between those with DED and group 2. A significant negative correlation was found of GCD with OSDI and with BUT (p<0.001; R=-0.795 and R=-0.756, respectively). CONCLUSION: Glaucoma therapy leads to a marked reduction of GCs, especially in the associative regimens. Given the negative correlation with tear film function tests, GCD reduction may play a pivotal role in the pathophysiology of the glaucoma-related disease of the ocular surface.

Three-dimensional Laser Scanning Confocal Analysis of Conjunctival Microcysts in Glaucomatous Patients Before and After Trabeculectomy.

BACKGROUND/AIM: In glaucoma, conjunctival epithelial microcysts (CEM) have been extensively investigated by means of laser scanning confocal microscopy. In the present case series, we examined eight glaucomatous patients undergoing trabeculectomy to obtain a 3-dimensional (3-D) characterization of CEM. MATERIALS AND METHODS: Image acquisition was performed in z-scan automatic volume mode by Heidelberg Retina Tomograph III/Rostock Cornea Module and a series of 40 images of 300×300 µm (384×384 pixels) to a maximum depth of 40 µm were acquired throughout the upper bulbar conjunctiva before (at the site planned for surgery) and eight weeks after trabeculectomy. The 3-D volume tissue reconstruction with maximal size of 300×300×40 µm was obtained. RESULTS: In the enface view, CEM appeared as empty, optically clear, round or oval shaped sub-epithelial structures. The 3-D spatial reconstruction showed microcysts as oval-shaped and optically clear elements, which were close, but clearly separated from the epithelium. CEM were embedded in the extra-cellular spaces and located about 10 µm below the epithelial surface. After trabeculectomy, CEM increased density and area especially along the horizontal axis. CONCLUSION: The 3-D in vivo confocal reconstruction of CEM permits for better clarification of their microscopic anatomy and patho-physiological significance, confirming their involvement in AH flow through the bleb-wall after filtration surgery for glaucoma.

Qualitative and Quantitative Assessment of Vascular Changes in Diabetic Macular Edema after Dexamethasone Implant Using Optical Coherence Tomography Angiography.

The aim of this study was to investigate retinal and choriocapillaris vessel changes in diabetic macular edema (DME) after the intravitreal dexamethasone implant (IDI) using optical coherence tomography angiography (OCTA). Moreover, a comparison between morphological and functional parameters of DME and healthy patients was performed. Twenty-five eyes of 25 type 2 diabetic retinopathy patients complicated by macular edema (DME group) and 25 healthy subjects (control group) were enrolled. Superficial capillary plexus density (SCPD) and deep capillary plexus density (DCPD) in the foveal and parafoveal areas, choricapillary density (CCD) and optic disc vessel density (ODVD) were detected using OCTA at baseline and after 7, 30, 60, 90 and 120 days post injection. Best corrected visual acuity (BCVA), retinal sensitivity, and central retinal thickness (CMT) were also evaluated in both groups of patients. A statistically significant difference between the two groups (DME and controls) was found in terms of functional (MP, p < 0.001 and BCVA, p < 0.001) and morphological (CMT, p < 0.001; SCPD in the parafoveal area, p < 0.001; DCPD in the foveal area, p < 0.05 and parafoveal area, p < 0.001; CCD, p < 0.001) parameters. After the treatment, SCPD and DCPD in the foveal and parafoveal areas did not modify significantly during the follow up.

In Vivo Confocal Imaging of the Conjunctiva as a Predictive Tool for the Glaucoma Filtration Surgery Outcome.

Purpose: To examine the preoperative conjunctival dendritic cell density (DCD), goblet cell density (GCD), and stromal meshwork reflectivity (SMR) in glaucomatous patients undergoing filtration surgery, using in vivo confocal microscopy (IVCM). Methods: Sixty-six patients were enrolled. At baseline, IVCM was performed at the site planned for surgery, and was repeated after 12 months at bleb site. Surgery was successful when a one-third reduction of baseline IOP was obtained at the last follow-up. The main outcomes were baseline DCD, GCD, and SMR, and 12 months IOP. The relations between baseline confocal parameters and 12 months IOP were analyzed. Results: Filtration surgery was successful in 43 patients (group 1: complete success, 25; group 2: qualified success, 18), and unsuccessful in 23 patients (group 3). Baseline IOP (mm Hg) was 27.6 ± 2.8, 28.8 ± 4.1, and 27.7 ± 3.2 in groups 1 to 3, respectively. Preoperative DCD and SMR were lower in group 1 compared with groups 2 (P < 0.001, P < 0.05), and 3 (P < 0.001); preoperative GCD was higher in group 1 compared with groups 2 and 3 (P < 0.001). DCD and GCD were also different between groups 2 and 3 (P < 0.05, P < 0.001). At 12 months, IOP reduced by 43.3%, 38.4%, and 15.8% in groups 1 to 3. Twelve-month IOP reduction negatively correlated with baseline DCD and SMR (P < 0.001, r = -0.786; P < 0.05, r = -0.618), and positively with GCD (P < 0.001, r = 0.752). Conclusions: Preoperative DCD, GCD, and SMR are parameters correlated with the filtration surgery outcome, with DCD presenting the strongest correlation. IVCM of the conjunctiva may represent an imaging tool to predict the surgical success in glaucoma.

The Conjunctiva-Associated Lymphoid Tissue in Chronic Ocular Surface Diseases.

Ocular surface diseases (OSDs) represent a widely investigated field of research given their growing incidence and the negative impact on quality of life. During OSDs, cytokines generated by damaged epithelia trigger and deregulate the lymphoid cells composing the eye-associated lymphoid tissues, inducing an immune-mediated chronic inflammation that amplifies and propagates the disease during time. The conjunctiva-associated lymphoid tissue (CALT), given its particular position that permits immune cells covering the cornea, might play a crucial role in the development of OSDs. Despite the recognized inflammatory role of mucosa-associated lymphoid tissues in other stations taking contact with the external environment (gut or bronchus), CALT did not gain the deserved consideration. In the last years, the diffusion of the in vivo confocal microscopy (IVCM) stimulated the interest to CALT, especially in dry eye, ocular allergy, and glaucoma. Though the initial stimuli were different, IVCM documented similar changes, represented by increased lymphoid cells within the diffuse layer, follicles and interfollicular spaces. These findings, which need to be validated by immunohistology, support the CALT stimulation during OSDs. However, while an involvement of the CALT in OSDs is hypothesizable, the exact role of this structure in their pathogenesis remains unclear and warrants further investigations.

Curcuma longa Is Able to Induce Apoptotic Cell Death of Pterygium-Derived Human Keratinocytes.

Pterygium is a relatively common eye disease that can display an aggressive clinical behaviour. To evaluate the in vitro effects of Curcuma longa on human pterygium-derived keratinocytes, specimens of pterygium from 20 patients undergoing pterygium surgical excision were collected. Pterygium explants were put into culture and derived keratinocytes were treated with an alcoholic extract of 1.3% Curcuma longa in 0.001% Benzalkonium Chloride for 3, 6, and 24 h. Cultured cells were examined for CAM5.2 (anti-cytokeratin antibody) and CD140 (anti-fibroblast transmembrane glycoprotein antibody) expression between 3th and 16th passage to assess cell homogeneity. TUNEL technique and Annexin-V/PI staining in flow cytometry were used to detect keratinocyte apoptosis. We showed that Curcuma longa exerts a proapoptotic effect on pterygium-derived keratinocytes already after 3 h treatment. Moreover, after 24 h treatment, Curcuma longa induces a significant increase in TUNEL as well as Annexin-V/PI positive cells in comparison to untreated samples. Our study confirms previous observations highlighting the expression, in pterygium keratinocytes, of nuclear VEGF and gives evidence for the first time to the expression of nuclear and cytoplasmic VEGF-R1. All in all, these findings suggest that Curcuma longa could have some therapeutic potential in the treatment and prevention of human pterygium.

Uveo-scleral outflow pathways after ultrasonic cyclocoagulation in refractory glaucoma: an anterior segment optical coherence tomography and in vivo confocal study.

AIMS: To evaluate, using anterior segment optical coherence tomography (AS-OCT) and in vivo confocal microscopy (IVCM), the uveo-scleral aqueous humour (AH) outflow pathways after ultrasonic circular cyclocoagulation (UCCC). METHODS: Forty-four patients with refractory glaucoma underwent 4 or 6 s UCCC (group 1, 24 eyes; group 2, 20 eyes). UCCC was successful when the preoperative intraocular pressure (IOP) reduced by one-third. AS-OCT and IVCM were performed at baseline and at month 1 to evaluate the sclera and conjunctiva. The main outcomes were mean intra-scleral hyporeflective spaces area (MIHSA: mm2) at AS-OCT, mean density and area of conjunctival microcysts (MMD: cysts/mm2; MMA: µm2) at IVCM. The relations between MIHSA, MMA and MMD with IOP were analysed. RESULTS: Mean baseline IOP was 26.9±2.8 mm Hg in group 1 and 27.5±4.0 in group 2. Intra-scleral hyporeflective spaces and microcysts were observed in both groups, without significant differences in MIHSA, MMA and MMD. At month 1, UCCC was successful in 63.6% of patients (41.6% in group 1, 80% in group 2), and IOP reduced to 18.8±3.2 (30.1%) and 17.1±2.7 mm Hg (38.7%), respectively (p<0.001). MIHSA showed a twofold and threefold increase in group 1 and 2 (p<0.05), with a significant difference between groups (p<0.05). MMA and MMD increased in both groups (p<0.05), with values higher in group 2 (p<0.05). Significant relations were found between MIHSA and IOP in both groups (p<0.01). CONCLUSIONS: UCCC induced anatomical modifications of sclera and conjunctiva, which suggested that the trans-scleral AH outflow enhancement is one of the possible mechanisms exploited by ultrasounds to reduce IOP.

Advance in the pathogenesis and treatment of normal-tension glaucoma.

Normal-tension glaucoma (NTG) is a multifactorial disease where mechanical stresses and vascular alterations to the optic nerve head probably represent the key pathogenic moments. Although intraocular pressure (IOP) plays a crucial role in the retinal ganglion cell loss, the IOP reduction does not necessarily reduces the disease progression. Therefore, several IOP-independent factors such as glutamate toxicity, oxidative stress, autoimmunity, and vascular dysregulation have been considered in the pathogenesis of NTG. Numerous evidences documented an impairment of the ocular blood flow, involved both in the onset and progression of the disease. The IOP reduction remains the main strategy to reduce the damage progression in NTG. Recently, new treatment strategies have been proposed to improve the control of the disease. Neuroprotection is a rapidly expanding area of research, which represents a promising tool. In the present review, we summarize the recent scientific advancements in the pathogenesis and treatment of NTG.

Optical Coherence Tomography Angiography in Retinal Vascular Diseases and Choroidal Neovascularization.

Purpose. To assess the ability of optical coherence tomography-angiography (OCT-A) to show and analyze retinal vascular patterns and the choroidal neovascularization (CNV) in retinal vascular diseases. Methods. Seven eyes of seven consecutive patients with retinal vascular diseases were examined. Two healthy subjects served as controls. All eyes were scanned with the SD-OCT XR Avanti (Optovue Inc, Fremont CA, USA). Split spectrum amplitude decorrelation angiography algorithm was used to identify the blood flow within the tissue. Fluorescein angiography (FA) and indocyanine green angiography (ICGA) with Spectralis HRA + OCT (Heidelberg Engineering GmbH) were performed. Results. In healthy subjects OCT-A visualized major macular vessels and detailed capillary networks around the foveal avascular zone. Patients were affected with myopic CNV (2 eyes), age-related macular degeneration related (2), branch retinal vein occlusion (BRVO) (2), and branch retinal artery occlusion (BRAO) (1). OCT-A images provided distinct vascular patterns, distinguishing perfused and nonperfused areas in BRVO and BRAO and recognizing the presence, location, and size of CNV. Conclusions. OCT-A provides detailed images of retinal vascular plexuses and quantitative data of pathologic structures. Further studies are warranted to define the role of OCT-A in the assessment of retinovascular diseases, with respect to conventional FA and ICG-A.

In vivo confocal microscopy of conjunctiva-associated lymphoid tissue in healthy humans.

PURPOSE: To investigate modifications with aging of the presence, distribution and morphologic features of conjunctiva-associated lymphoid tissue (CALT) in healthy human subjects using laser scanning in vivo confocal microscopy (IVCM). METHODS: A total of 108 (age range, 17-75 years) subjects were enrolled. In vivo confocal microscopy of the tarsal and bulbar conjunctiva, and impression cytology (IC) with CD3 (intra-epithelial T-lymphocytes) and CD20 (intra-epithelial B-lymphocytes) antibody immunofluorescence staining were performed. The main outcomes were subepithelial lymphocyte density (LyD), follicular density (FD), and follicular area (FA). The secondary outcomes were follicular reflectivity (FR), and lymphocyte density (FLyD), and CD3 and CD20 positivity. RESULTS: Conjunctiva-associated lymphoid tissue was observed in all subjects (97% only superior and 3% in both superior and inferior tarsum). Lymphocyte density ranged from 7.8 to 165.8 cells/mm(2) (46.42 [18.37]; mean [SD]), FD from 0.5 to 19.4 follicles/mm(2) (5.3 [3.6]), and FA from 1110 to 96,280 mm(2) (26,440 [26,280]). All three parameters showed a highly significant inverse cubic relationship with age (P < 0.001); that is, in the first and last parameters a steep decline up to 35 years and above 65 years of age, with a plateau phase between these ages, whereas FA had a gradually decreasing rate of loss over the studied age range. CD3 and CD20 IC were consistent with these results. CONCLUSIONS: In vivo confocal microscopy was effective in revealing CALT and modifications these structures undergo with aging. Aging correlated with an involution of all parameters defining lymphoid structures. These modifications may account for the decrease of mucosal immune response and increase of ocular surface diseases in the elderly.

Trans-conjunctival aqueous humor outflow in glaucomatous patients treated with prostaglandin analogues: an in vivo confocal microscopy study.

PURPOSE: To analyze, using in vivo laser scanning confocal microscopy (LSCM), the conjunctival features in glaucomatous patients receiving prostaglandin analogues (PGA). METHODS: Eighty eyes of 80 consecutive glaucomatous patients naive for therapy were enrolled; 30 eyes of 30 healthy subjects served as a control. Patients were randomized to: preservative-free (PF) and preserved latanoprost (groups 1 and 2, respectively), PF and preserved timolol (groups 3 and 4), and controls to vehicle of latanoprost or physiological buffered saline solution (groups 5 and 6). All subjects underwent LSCM of bulbar conjunctiva at baseline and 3 months after initiating therapy. The main outcomes were: mean density (MMD: cysts/mm(2)) and mean area (MMA: cysts/mm(2)) of epithelial microcysts. The relations between MMA and MMD with intraocular pressure (IOP), age, and mean defect (MD), were analyzed. RESULTS: At baseline, microcysts were found in all subjects. At month three, MMD did not change in all groups (p > 0.05). MMA significantly increased only in group 1 from 2,158.81 ± 524.09 to 3,877.77 ± 867.31, and in group 2 from 2,019.71 ± 541.03 to 5,560.39 ± 1,176.14, with values significantly higher in group 2 (p < 0.001). Significant relations were not found between MMD and MMA with IOP, MD, and age (p > 0.05). CONCLUSIONS: PGA increased MMA in therapy-naive glaucomatous patients, indicating a possible enhancement of the trans-conjunctival aqueous humor outflow. Therefore, conjunctiva seems an additional target tissue to evaluate the hydrodynamic pathways in glaucoma and modifications induced by medical therapy.

Ibopamine: D1-dopaminergic agonist in the diagnosis of glaucoma.

PURPOSE: The purpose of the study was to assess the effect of ibopamine (3,4 di-isobutyrrylester of N-methyldopamine), a D1-dopamine agonist, on intraocular pressure (IOP) in offspring of parents with primary openangle glaucoma as a consequence of outflow structures impairment. MATERIALS AND METHODS: We included participants aged between 8 and 40 years: group 1, 163 offspring of at least 1 parent with primary openangle glaucoma with normal IOP and without glaucomatous damages; group 2, 108 offspring of healthy parents (without history or existing glaucoma). Ibopamine test was performed by instilling 2 drops, 5 minutes apart, in both eyes followed by repeated IOP measurements over a 45-minute period. The test is considered positive if there is an IOP increase of ≥3 mm Hg 45 minutes after instillation. RESULTS: Baseline IOP before the test was 15.73±2.31 and 15.31±1.86 mm Hg in groups 1 and 2, respectively. Test was positive in 44.33% of cases in group 1 with a mean increase in IOP of 5.57 mm Hg (P<0.001), whereas in all participants of group 2 the test was negative with even 1 to 2 mm Hg IOP reduction. CONCLUSIONS: D1-dopaminergic stimulation due to ibopamine increases IOP as a result of increased production of the aqueous humor in participants with an impaired outflow. The study showed that offspring of at least 1 parent with primary openangle glaucoma--offspring without glaucomatous damages--show an increase of IOP after ibopamine administration, which signifies an impaired function of outflow structures and, therefore, a predisposition to intraocular hypertension and possible glaucoma.

Conjunctival findings in hyperbaric and low-tension glaucoma: an in vivo confocal microscopy study.

PURPOSE: To analyse the epithelial features of the bulbar conjunctiva in hyperbaric and low-tension glaucoma (LTG) using in vivo confocal microscopy (IVCM). METHODS: Thirty-six eyes of 36 patients [18 affected by primary open-angle glaucoma (POAG) and 18 with LTG] were studied; control group was constituted by 28 eyes of 28 healthy subjects. All eyes were examined using digital confocal laser-scanning microscopy (HRT II Rostock Cornea Module). The main IVCM outcome measurements were mean density (MMD: cysts/mm(2)) and mean total area (MMA: µm(2)) of the epithelial microcysts. RESULTS: The mean intraocular pressure level (mmHg ± SD) was 15.1 ± 1.7, 16.3 ± 3.1 and 12.6 ± 1.8 in healthy, POAG and LTG eyes, respectively. Conjunctival microcysts were found in all patients and subjects: for healthy subjects, MMD = 10.9 ± 11.1 cysts/mm(2) and MMA = 1501.9 ± 1191.1 µm(2); for patients infected with POAG, MMD = 36.8 ± 28.6 cysts/mm(2) and MMA = 7904.8 ± 7050.5 µm(2); and for patients infected with LTG MMD = 45.6 ± 29.0 cysts/mm(2) and MMA =7946.9 ± 5227.5 µm(2). MMD and MMA were not significantly different between patients infected with POAG and those with LTG, whereas they were significantly greater in patients (fourfold and fivefold, respectively) than healthy subjects. CONCLUSIONS: The present study demonstrated that conjunctival microcysts represent an in vivo feature in all eyes with medically controlled POAG and LTG. Therefore, conjunctiva deserves careful analysis, because its accurate microscopic definition could help clarify the pathophysiology of aqueous outflow in glaucoma.