Rebound macular edema following oral acetazolamide therapy for juvenile X-linked retinoschisis in an Italian family

BACKGROUND: Juvenile X-linked retinoschisis (RS1, OMIM: 312700) is a hereditary vitreoretinal dystrophy characterized by bilateral foveal schisis and, in half of the patients, splitting through the nerve fiber layer in the peripheral retina. In the first decade of life, patients usually develop a decrease in visual acuity. Long-term visual outcomes can be poor due to the limited number of known successful treatments. PURPOSE: The purposes of this study were to present, for the first time, a p.Arg197Cys missense mutation in the RS1 gene (OMIM: 300839) in a four-generation Italian family with RS1 and to examine the clinical response to the treatment with acetazolamide tablets alone or in combination with dorzolamide eye drops as assessed by spectral-domain optical coherence tomography (SD-OCT). METHODS: Eleven individuals, including two brothers with RS1 (patients 1 and 2), underwent a full medical history examination and a comprehensive ocular assessment that involved SD-OCT, fluorescein angiography, electroretinography and DNA analysis. Each RS1 patient received oral acetazolamide (375 mg daily) during the first three months. Thereafter, patient 1 continued only with dorzolamide eyedrops three times a day for a period of three months, while patient 2 spontaneously stopped both medications. RESULTS: Sequence analysis of the RS1 gene identified a hemizygous c.589C>T (p.Arg197Cys) missense mutation in exon 6, which has not been previously reported in an Italian family. A different response to the medical therapy was observed in the four eyes of the two affected brothers hemizygous for this abnormality. Of note, after acetazolamide interruption, a rebound effect on cystoid macular edema reduced the beneficial effects of the initial therapy for RS1 from p.Arg197Cys mutation. Indeed, a minimal rebound effect on cystoid macular edema, and an improvement in visual acuity, was observed in patient 1 during the six months of treatment. Conversely, in patient 2, an initial improvement in cystoid macular edema was not associated with visual acuity changes, followed by a marked rebound effect. CONCLUSION: This study showed that the sequential use of acetazolamide tablets and dorzolamide eye drops should be considered and studied further as a possible treatment for macular edema and visual impairment in patients with RS1 from a hemizygous p.Arg197Cys mutation

X-linked retinoschisis: OCT-angiography in two brothers from a four-generation family with a p.Arg197Cys pathogenic variant in the RS1 gene

Introduction X-linked juvenile retinoschisis (XLRS) is a rare genetic disease causing retinal splitting. The aim of this work is to describe the optical coherence tomography angiography (OCTA) features in two brothers affected by an hemizygous c.589C>T (p.Arg197Cys) pathogenic variant in exon 6 of the RS1 gene. Case decription Each patient underwent a complete ophthalmological examination, including measurement of best corrected visual acuity, slit-lamp biomicroscopy, fundus color photographs, fundus autofluorescence and infrared imaging, fluorescein angiography, spectral-domain optical coherence tomography (SD-OCT) and optical coherence tomography angiography (OCTA). En Face SD-OCT and OCTA revealed the presence of two different pattern of cystic lesions, fusiform and oval, disposed on a petaloid or irregular manner in the perifoveolar area. A widening of the foveal avascular zone with interruption of the vascular arcades was clearly evident. Furthermore, a capillary drop-out was observed in the superficial plexus of the central retina, other than capillary ectasia in the deep capillary plexus. Straight gray lines were visible among the cysts. Conclusions OCTA data herein described allow a detailed morphological evaluation of XLRS other than a quantitative assessment of retinal capillary flow in this disease. The retinal alterations that we have reported may be helpful to better understand this rare condition with OCTA being a sensitive technique to monitor the evolution of the disease and the response to potential future therapeutic approaches aimed to restore vision

The role of axial length (AxL) in planning strabismus surgery

Purpose: To discuss the importance of axial length (AxL) in strabismus surgery and the utility of its association to preoperative deviation data, in calculating the amount of recession to perform in patients affected by convergent strabismus. Methods: Case files of 28 patients, affected by non accommodative esotropia, who underwent recession of one or both medial rectus, in our department between 2009 and 2011, were analyzed. Subject age, data regarding pre and post-intervention angle of deviation for near (ND) and far distance (FD), and axial length (IOL Master, Carl Zeiss, Jena, Germany) were all evaluated. Post operation angle of deviation was evaluated after 3 months from intervention. Results: The patients have been divided in two groups in relation to mean AxL (21.78 mm): the former group had less than 21.78 mm, the second a longer AxL. Results have been evaluated as percent reduction of deviation, between pre- and post-operation. Percent reduction in shorter AxL was 66.37% (ND)and 68.22% (FD); reduction in longer AxL was 81.78 % (ND) and 87.09% (FD) Conclusion: Our results show that the recession of an extraocular muscle is more effective in a larger eye than in a small one. Axial length seems to be an import factor in predicting results of strabismus surgery and should be routinely obtained before any operation, in order to increase the amount of recession in shorter eyes. A large number of dose-response curves have been proposed over time as well the mechanisms that underlie a satisfactory outcome. According to different investigators, preoperative deviation appears to be the most important parameter that must be take into account before strabismus surgery. Importance, besides, has been given to globe size considering both axial length and external surface, but in many reports, conclusions do not agree with our clinical experience

OCT angiography in adult primary rhegmatogenous retinal detachment before and after vitreoretinal surgery

Purpose : To analyze the morphological characteristics of adult primary rhegmatogenous retinal detachment ( RRD) assessed by optical coherence tomography angiography (OCT-A) before and after 25 gauge pars plana vitrectomy(25 G PPV), with gas or silicone oil tamponade. Methods : Retrospective review all RDD surgeries performed between june and october 2016 with anatomical success, defined as a complete retinal attachment,. All patients underwent a complete ophthalmological examination, including fundus photography, spectral-domain OCT ( Cirrus 5000 SD-OCT, Zeiss, Germany) and OCT-A (Optovue XR Avanti, Optovue, USA), before and at follow-up visits ranging from 1 month to 6 months after RRD surgery. OCT-A retinal capillary density flow analysis was performed at four main depth intervals: 1) the superficial capillary plexus, acquired with automatic segmentation , 2) the deep capillary plexus, 3) photoreceptors ,and 4)choriocapillaris , all acquired with manual segmentation. Statistical analysis was performed by means of Mann Whitney U test and Wilcoxon W test. Results : Fifty-one eyes of 51 patients were analyzed. Operative procedures included pars-plana vitrectomy 25 G, exchange BSS/PFCL , endolaser, and intraocular tamponade with 50% sulfur hexafluoride gas in 36 eyes, and silicone oil in 15 eyes. Forty-five eyes were macula off and six eyes were macula on. Before surgery, in macula-off patients we observed a marked reduction of capillary flow in superficial, deep and choriocapillary layers. After surgery, in macula-off patients, SD OCT demonstrated the presence of foveolar lucencies in 17% of cases, while OCT-A revealed enlargement and irregular changes of the foveal avascular zone ( FAZ ), and a residual significant hypoperfusion at the level of outer retina and photoreceptors. In macula-on patients, no lucencies were detected, and a subtle hypoperfusion of all retinal layers, less severe than in macula-off cases, was apparent at OCT-A. Conclusions : OCT-A is a noninvasive imaging modality that allows visualization of retinal capillary density flow changes occurring after surgery for retinal detachment, and it could represent a predictive tool of visual acuity and retinal sensitivity recovery after 25 G PPV with gas or silicone oil tamponade

Evaluation of the adhesive properties of the cornea by means of optical coherence tomography in patients with meibomian gland dysfunction and lacrimal tear deficiency.

The aim was to determine the influence of meibomian gland dysfunction (MGD) and aqueous tear deficiency dry eye (ADDE) on the adhesive properties of the central cornea by means of optical coherence tomography (OCT), and to investigate the relationship between corneal adhesiveness and classical tear tests, as well as the reliability of results, in these lacrimal functional unit disorders.Prospective, case-control study.Twenty-eight patients with MGD and 27 patients with ADDE were studied. A group of 32 healthy subjects of similar age and gender distribution served as a control group. The adhesive properties of the anterior corneal surface were measured by OCT, based on the retention time of adhesion marker above it, in all participants.An excellent (≥5 minutes), borderline (within 3-5 minutes), fair (within 1-3 minutes) and poor (<1 minute) values of corneal adhesiveness were found, respectively, in 0%, 7.1%, 64.3% and 28.6% of MGD, in 0%, 7.4%, 63% and 29.6% of ADDE, and in 31.3%, 65.6%, 3.1% and 0% of healthy patients. The differences in time of corneal adhesiveness between MGD and healthy patients, as well as between ADDE and healthy patients, were found to be statistically significant (p<0.001; p<0.001; respectively). Conversely, no statistical significant differences between MGD and ADDE were found (p = 0.952). Data analysis revealed a statistically significant correlation between corneal adhesiveness and clinical tests of dry eye, as well as an excellent degree of inter-rater reliability and reproducibility for OCT measurements (p<0.001).ADDE and MGD share similar abnormalities on OCT imaging. Decreased adhesive properties of the anterior cornea were identified as a common feature of MGD and ADDE. This simple OCT approach may provide new clues into the mechanism and evaluation of dry eye syndrome

Classification system of clearance of lipids in human tears according to optical coherence tomography parameters

Purpose: To establish a classification system for clearance of lipids (CoL) in human tears according to optical coherence tomography (OCT) parameters. The purpose of this classification system is to provide a uniform and objective assessment of the dynamics of tear lipids with a novel technique of contrast-enhanced optical coherence tomography imaging in evaluation of CoL. Methods: The CoL appearance grading scale contains a set of OCT images standards illustrating a range of various concentrations of lipids in human tears (0.5%, 0.25%, 0.125%, 0.06%, 0%). These standards consist of OCT scans of the lower tear meniscus (LTM) at baseline and after instillation of a lipid-based tracer (containing different concentrations of lipids) or saline. Fifty-one OCT images were evaluated and scored by three cornea subspecialists in a masked fashion according to the scale. Results: High inter-observer agreement was found using the scale to classify the CoL, with respect to the appearance of OCT reflectivity (CoL +0.90, interclass correlation coefficient for consistency using a 2-way mixed effect model). Conclusions: The CoL appearance grading system is a simple, reproducible system for classifying the OCT appearance of turnover of lipids in human tears

Humphrey visual field 10-2 and macular retinal thickness correlations in glaucomatous patients.

Purpose:To provide a quantitative comparison between the macular retina thickness (MRT) and the Humphrey visual field (HVF) 10-2 SITA-standard strategy parameters in glaucomatous patients. Methods:Retrospective statistical analysis of spectral domain optical coherence tomography macular cube scans 512x128 (Cirrus HD-OCT 4000, Carl Zeiss Meditec, Inc. , Dublin, CA) compared with HVF mean deviation (MD) and pattern standard deviation (PSD) in sixty eyes of thirty-six glaucomatous subjects. Abnormal MRT on OCT was defined as an average macular thickness value of any one of four quadrants to be less than 5% of normative database. Results:Eighteen (30% ) glaucomatous eyes showed an abnormal MRT. In patients with reduced MRT the mean was 236,8 μm, whereas in patients with normal MRT the mean was 264,3 μm. In eleven eyes with MRT reduction the average MD was -10,56 dB, and PSD was greater than 2,5 dB in seven of these eleven eyes. In 61% of glaucomatous patients there was a correlation between MRT and MD. Conclusions:In glaucomatous patients, OCT macular retinal thickness analysis may help in detecting the existence of a visual field defec

Shifting and sliding of medial-inferior conjunctival flap for surgical treatment of Pterygium

Purpose:To describe a novel surgery technique in the treatment of primary pterygium and to evaluate its safety and rate of recurrence. Methods:Retrospective case series. Between January 2012 and October 2013, escluded summer months, 128 patients, of which 103 were men and 25 women, all living in Sardinia (Italy) were operated on for a primary nasal pterygium. The mean age was 55,61 ± 9,93 (range 33-75). Pterygium excision was combined with a sliding and shifting congiuntival flap technique. The flap harvested from the medial inferior bulbar conjunctiva was placed over the bare sclera and glued with Tisseel (Baxter AG, Vienna), a human tissue glue. Topical and oral steroids and antibiotic eyedrops were prescribed, and the eye was patched for 1 day. Results:Patients were followed up for at least 1 year, and the outcomes and recurrence rates were evaluated. In case of fibrovascular regrowth, it was manifested by third month of follow up, but progression arrested before sixth month control. Six patients showed a corneal invasion between 1 and 2.5 mm beyond the limbus, in 1 patient the new fibrovascular tissue was 4.5 mm . The recurrence rate estimated at 1 year after surgery was 5.46%. No intraoperative complication was observed. The mean surgery time was 10.30’’ ± 1.30” minutes. Conclusions:The sliding and shifting congiuntival flap technique is a safe alternative in pterygium surgery for preventing recurrence. It is technically easier than congiuntival autograft and reduces operative time. Moreover the low rate of recurrence could be positively influenced by the reduced inflammatory reaction due to the absence of a congiuntival suture

Fibroblasts isolated from human pterygia exhibit altered lipid metabolism characteristics

To determine whether the fibrovascular proliferation observed in pterygium, may be, at least in part, mediated by an increased activity of cholesterol metabolism. The correlation between lipid metabolism and rate of growth was studied in human normal conjunctival (NCF) and primary pterygium fibroblasts (PFs) in primary culture. The expression of two proliferation markers (Ki-67 and p53) was evaluated by immunohistochemical staining techniques. Proliferation was evaluated by [(3)H]thymidine incorporation and by immunohistochemical assays. Lipid metabolism was evaluated by (14)C-oleate incorporated into cholesterol esters as well as by oil red O staining. Moreover, the cultures of pterygium fibroblasts were supplemented with two antiproliferative drugs in order to confirm the effective alterations in cholesterol metabolism related to proliferation. Immunohistochemistry of frozen sections from primary pterygium demonstrated an increased staining in Ki-67 and p53 compared with staining observed in normal conjunctiva. A dramatically increased activity of intracellular cholesterol metabolism was demonstrated in pterygium fibroblasts obtained from four different patients. This finding was confirmed by the reduction of cholesterol metabolism in pterygium fibroblasts treated with antiproliferative drugs. Collectively, these data support the hypothesis that alterations of cholesterol metabolism are involved in the development of pterygia. This finding may represent a target of new therapeutic approaches for treatment and prevention of pterygium