bluuebunny/crossref_metadata_2025 huggingface dataset:
Anatomic response of occult choroidal neovascularization to intravitreal ranibizumab: a study by indocyanine green angiography
Authors: TRAN THC , QUERQUES G
Published: August 2012

Purpose To investigate changes in indocyanine green angiography (ICGA) features of occult choroidal neo‐vascularization (CNV) after intravitreal ranibizumab injections.

Methods We reviewed the charts of all consecutive patients with newly diagnosed occult CNV secondary to age‐related macular degeneration (AMD) treated by intravitreal ranibizumab. In all patients, optical coherence tomography(OCT) and ICGA were performed at baseline, after 3 months and 12 months.

Results Fifty‐one eyes of 44 patients (ten males, 34 females, mean age 77.8±7.3 years) were included. Mean follow‐up was 20.3±6.2 months. During the first 12 months, patients received 5.5±2.7 intravitreal ranibizumab injections.When compared with baseline, best‐corrected visual acuity(BCVA) significantly improved at the 3‐month follow‐up visit(60.5 ±22.0 vs 50.9 ±20.7 letters, p=0.04), and stabilized at 12‐month visit (55.7 ±18.2 letters; p=0.05). Central macular thickness (CMT) significantly improved during follow‐up (229±54.7µm vs 281±61.3 µm at baseline, p=0.003). An overall stabilization was observed on ICGA in both the lesion area (5.27±3.9 mm2 at baseline vs 4.60±3.5 mm2 at month 12, p=0.4), and greatest linear dimension (GLD 2.66±1.2 mm at baseline vs 2.55±1.0 mm at month 12, p=0.3). Eight eyes (15.7%) showed CNV growth on ICGA (lesion area 3.98±3.2 mm2 at baseline vs 4.3±2.7 mm2 at month‐12,p=0.6; GLD 2.11±1.0 mm at baseline vs 2.70±0.8 mm at month‐12, p=0.05).

Conclusion ICGA suggests that functional outcomes after intravitreal ranibizumab is related to CMT reduction rather than CNV regression
Integrated imaging approach in RAP diagnosis
Authors: PARRAVANO M , VARANO M , VIRGILI G
Published: August 2012

Purpose to explore the inter‐observer agreement in the diagnosis of retinal angiomatous proliferation (RAP) using fluorescein (FA) and indocyanine green angiographies (ICGA) and to detect which morphological features of the neovascular lesion are associated with RAP diagnosis.

Methods cross‐sectional study. Consecutive patients with newly diagnosed neovascular AMD evaluated in 8 Retina Centres have been considered. FA and ICGA were obtained in all centres according to a standard protocol, both performed either as a static or as a dynamic examination. All images were graded by two observers from different institutions.

Results 201 eyes with neovascular AMD of 155 consecutive patients (mean age: 76±8 years) have been considered. Overall RAP prevalence was 30% using FA and 26% using ICGA. Patients studied with dynamic angiography were twice more likely to be diagnosed RAP as those using static angiography. Inter‐observer agreement for the overall detection of RAP was high using FA (kappa: 0.868; 95%CI: 0.793‐0.944) and very high using ICGA (kappa: 0.905; 95%CI: 0.836‐0.974). The agreement between the two observers tended to be higher for the truncated vessel than for the anastomosis in FA as wells as in ICGA, but no comparison yielded statistical significance (p=0.258 and p=0.584, respectively).

Conclusion the inter‐observer agreement for RAP detection was very good both using FA and ICGA, but the overall detection of RAP was higher for dynamic strategy compared with static one.
Keratoconus patterns and intrastromal segments
Authors: BARRAQUER RI , ALFONSO J , MURTA J
Published: August 2012

Purpose Intrastromal corneal segments (ICS) are a popular alternative for the treatment of keratoconus. However, its variability makes difficult a simple approach to ICS implantation. The SA.ANA classification of ICS implant modalities was developed to enable comparability between case series, with implications on the best ICS combinations for the different keratoconus patterns.

Methods A multicenter database was established including ICS implanted during the 2004 to 2011 period. Based on 1097 cases, a simple classification of ICS implantation modalities was devised using 2 basic criteria: symmetry and axiality, whose combination results in 4 major types. The observed series was fitted into this framework.

Results 2 equal ICS facing each other define symmetrical (S) implantation. Asymmetrical (A) means only 1 or 2 different ICS. Axial (A) implants are those placed with their center at the flatter astigmatism axis, while non‐axial (NA) refers to those at an axis differing ≥30º from that of astigmatism. This results in 4 main types (SA, AA, SNA, ANA), while the asymmetric types can include 1 or 2 ICS (AA1, AA2, ANA1, ANA2). The most frequent modality was asymmetrical‐axial (AA) totaling almost 70% of the implants. Symmetric‐axial (SA) represent about 10%. The non‐axial groups account for the remaining minority (20%).

Conclusion The SAANA classification employs simple criteria for a comprehensive description of the ICS implantation types. Identifying these types is a prerequisite for a meaningful comparison of the clinical results. This classification is also useful as a guideline to select the best ICS combinations for a particular keratoconus case. While axial implantation constitutes 80% of the cases, the non‐axial types may address special problems as non‐coincident astigmatism & coma.

Commercial interest
Cross linking for keratoconus ‐ clinical results comparing epithelium removal versus no removal
Authors: CAPOROSSI ALDO , MAZZOTTA C , PARADISO AL
Published: August 2012

Purpose Comparative prospective mid‐term 24 months functional analysis after Epi‐off and Epi‐on Riboflavin UV A corneal cross‐linking (CXL) in patients affected by progressive keratoconus (KC).

Methods Functional analysis comprised 30 eyes of 24 patients (15 ‐ 26 years) treated by epi‐on trans‐epithelial CXL procedure and 30 eyes of 24 patients (10 ‐ 26 years) treated by standard epi‐off CXL. Therapy was performed according to the Siena protocol by using the Vega CBM (Caporossi‐Baiocchi‐Mazzotta) X linker (CSO, Florence, Italy) at Siena University.

Results At 24 months follow‐up patients showed a mean gain in UCVA of +0.2, +Snellen lines in the epi‐off group while in the epi‐on group after a mean improvement of 1 Snellen Line at 3 months, uncorrected visual acuity gradually returned to baseline. BSCVA gained by a mean of +0.2 Snellen lines in the epi‐off procedure while in the epi‐on patients no significant improvement was recorded at 24 moths follow‐up. Kmax was reduced by a mean value of −0.6D, and Coma values improved by a mean of −0.45 μm in the epi‐off group. No significant variation in K readings and coma values were recorded in the epi‐on treatment.

Conclusion Epi‐off CXL showed a constant improvement of functional data while the epi‐on procedure showed a relative instability with a regression of functional outcomes returning to baseline at 24 months of follow‐up. In patients with progressive keratoconus under 26 years with corneal thickness over 400 microns epi‐off cross‐linking should be the first choice therapy. According to actual limitations epi‐on procedure should be reserved in patients over 26 years with low KC progression or in patients with thinnest point under 400 microns.
Assessment of dry eye after LASIK by real‐time measurement of higher order aberrations variation
Authors: GICQUEL JJ , DJABAROUTI M , ZAKARI W , BREMOND‐GIGNAC D , PISELLA PJ
Published: August 2012

Purpose To evaluate tear break‐up time (BUT) with real‐time (RT) higher order wavefront aberrations (HOA) measurements in myopic patients after Laser‐Assisted In Situ Keratomileusis (LASIK) surgery.

Methods HOA up to the sixth order for a 4‐mm pupil were measured in 20 normal subjects (Group 1) and in 20 myopic patients, with no history of dry eye (DE), before and after LASIK surgery (Group 2), using the IRX3 (Imagine Eyes, Orsay, France) Hartmann‐Shack (H‐S) aberrometer. The HOA measurements were performed (in triplicate) with a new dedicated software, once every second for up to 20 seconds. HOA variations were compared with the BUT by the conventional fluorescein method (CFM).

Results Twenty percent of the patients from Group 2 were complaining from DE symptoms. There was an excellent correlation between the HOA variation and the BUT recorded by the CFM in both groups. Reproducibility of the HOA measurements in all subjects and patients was excellent. BUT was significantly decreased (P<0.005) in 30% of the patients in Group 2 when compared to the normal tests subjects (Group 1).

Conclusion HS aberrometry is a non invasive method that has been used for the last decade for the assessment of the quality of vision, in patients undergoing refractive surgery and cataract or clear lens extraction. Studying the HOA variation is a new interesting method for evaluating both the quality vision and the BUT in patients after LASIK surgery.
Pathogenetic evaluation of the ocular surface drug correction in patients before LASIK
Authors: SERGEEVA M , KOVALEVSKAYA M , CHERNIKOVA I
Published: August 2012

Purpose Development and evaluation of the method of optimizing the ocular surface before the refractive intervention.

Methods Overall, 485 patients were enrolled in this case‐control study. Assessed the ocular surface, tear film and tear production before and after optimization of preoperative LASIK patients in 4 groups. Group 1 (A) ‐ high myopia ‐ (97), aged 18 to 35 years, group 2 (B) ‐ medium myopia – (145), aged 18 to 35 years, group 3 (C) ‐ myopia medium or high – (73), older than 35 years, group 4 (D) ‐ hypermetropia medium or high ‐ (49), older than 35 years. The criteria for preoperative drug correction of refractive surgery to the stage were the following diagnostic blocks: clinical data in diagnosis of dry eye and corneal status, corneal thickness, the definition of clinical refraction, including patient age, antioxidant and immune activity of tears.

Results The use of a preparation containing hydroxypropylguar and sorbitol in groups A and D, and a preparation containing hydroxyproylguar in groups B and C before LASIK reduces the number of complications refractive surgery.

Conclusion The correlation between the choice of ocular surface drug correction and the evaluation of the Norn, Lipkof, cornea vital coloring tests, cornea thickness (mm), the type of refractive error and degree of change (and its degree of myopia), the patient's age (35 and older than 35 years of age), antioxidant and immune activity of tears (the concentration of peroxyredoxin 6 (PRDX6), the presence or absence of gamma globulin).
Secreted frizzled proteins in control and keratoconus (KC) tears and corneas
Authors: MADIGAN MC , YOU JJ , WEN L , HODGES C , ROUFAS A , MCAVOY JW , SUTTON G
Published: August 2012

Purpose To investigate the expression and distribution of Wnt pathway antagonists, secreted frizzled‐related proteins (SFRPs), in tears and corneas from control and keratoconus (KC) patients.

Methods Immunofluorescence and confocal microscopy were used to examine the expression patterns of SFRP1, 2, 3, and 5 in paraffin sections of KC (n=11) and control (n=7) corneas. A custom SFRP1 ELISA was developed and used to quantify SFRP1 concentration in basal tear samples collected from KC (n=10) and control patients (n=10). The percentage SFRP1 of total tear protein concentration (%SFRP1) was calculated and compared between KC and control groups.

Results Immunofluorescence showed heterogeneous epithelial SFRP1 expression in all KC corneas compared to low expression in controls. SFRP3 and SFRP5 showed unique patterns of immunolabelling. SFRP3 was localised to epithelial cell membranes and limbal vessels in control corneas; cell membrane and cytoplasmic immunolabelling, and increased expression centrally, was seen in KC. SFRP5 was expressed strongly in the corneal stroma (KC and control). SFRP2 immunoreactivity not obvious in either control or KC corneas. ELISA results showed that tear SFRP1 levels were lower in KC compared to control tears.

Conclusion The pathogenesis of KC remains poorly understood. Our current study shows that SFRP1, 2, 3 and 5 are differentially expressed in control and KC corneas, consistent with previous work, suggesting Wnt signalling involvement in KC. The decreased levels of KC tear SFRP1 contrasts with increased expression in KC corneal epithelium, and may suggest KC‐associated differences in tear secretion or tear protein breakdown. Funded in part by Sydney Eye Hospital Foundation
Diagnostic ability for glaucoma of imaging technologies based on optic nerve head parameters
Authors: GIL ARRIBAS L , ARA M , FERRERAS A , SATUE M , BAMBO M , FERRANDEZ B
Published: August 2012

Purpose To assess the ability of optic nerve head (ONH) parameters measured with 2 different imaging technologies to discriminate between normal and glaucoma patients with visual field losses.

Methods Sixty‐seven normal eyes and 43 glaucoma patients were consecutive and prospectively selected. Participants were classified depending on the results of standard automated perimetry (SAP) and intraocular pressure. All of them underwent a comprehensive ophthalmic examination, at least 2 reliable SAP tests, and imaging of the ONH with the Heidelberg Retina Tomograph 3 (HRT; Heidelberg Engineering, Heidelberg, Germany) and with Cirrus OCT (Carl Zeiss Meditec, Dublin, Ca). Only one eye per subject was randomly included in the statistical analysis. The areas under the receiver operating characteristic curve (AUCs) were plotted and sensitivity‐specificity pairs compared.

Results The mean age was 55.713.6 years for the normal group and 59.16.2 years for the glaucoma group (p=0.133). The mean deviation of SAP was ‐0.71.2 dB and ‐5.96.1 dB (p<0.001) for the normal and glaucoma groups, respectively. The largest AUCs were observed for the rim area of Cirrus (0.954; 95% confidence interval [CI]: 0.919‐0.989), and the vertical cup/disk ratio of HRT3 (0.924; 95% CI: 0.890‐0.959). There was not a significant difference between them. Sensitivity at 85% fixed specificity was 86% for the rim area of Cirrus and 83.7% for the cup/disk area ratio of HRT3.

Conclusion ONH parameters measured with spectral‐domain OCT and HRT3 have similar diagnostic performance. OCT, however, does not require prior manual outlining of disc boundaries, reducing the dependency on operator skill.
Biomechanical response of lamina cribrosa and prelaminar tissue to an acute induced IOP elevati
Authors: GIZZI C , CELLINI M , CAMPOS EC
Published: August 2012

Purpose We decided to investigate the effects of an acute induced IOP elevation on the prelaminar tissue and on the lamina cribrosa in glaucomatous eyes and in healthy eyes by means of an high resolution Spectral Domain (SD) OCT.

Methods We enrolled 10 patients (mean age 70.2 years) affected by primary open angle glaucoma (POAG) and 10 healthy subjects (mean age 70.8 years) as controls. All the subjects were scanned with a SD‐OCT with real‐time eye tracking at baseline and in the same exact position during IOP elevation performed with an ophthalmodynamometer. The IOP was measured with a Tono‐Pen at baseline and during IOP elevation. The SD‐OCT images acquired were processed with a computer graphical suite to determine the prelaminar tissue displacement (PTD) and the laminar displacement in the two groups. An analysis of variance was used for evaluating group differences considering statistically significant a P < 0.05.

Results Baseline IOP was significantly different in the two groups, with higher values in patients compared to controls: 18.9(4.3) vs. 15.7(2.6) mmHg (P<0.037). Mean PTD was significantly lower in glaucomatous eyes compared to healthy eyes: 6.8(13.7) vs. 20.8(17.5) micron (P<0.039); whereas LD was similar in the two groups: ‐0.5(3.7) vs. 0.2(2.0) micron (P=0.366), and not statistically different from 0 (P=0.366).

Conclusion The study shows that an acute induced elevation of IOP does not induce a detectable movement of the lamina cribrosa anterior surface both in glaucomatous and healthy eyes.On the other hand the displacement of the prelaminar tissue is lower in patients with POAG than in controls.
Advanced open angle glaucoma with controlled intraocular pressure and cataract: one‐year predictive model of glaucoma progression after surgical treatment.
Authors: LIASKA A , PAPAKONSTANTINOU D , THEODOSIADIS P , CHATZISTEPHANOU K
Published: August 2012

Purpose To identify the predictive factors of midterm postoperative course in patients with visually significant cataract and advanced open angle glaucoma with intraocular pressure controlled on topical medications.

Methods 55 patients with visually significant cataract and advanced open angle glaucoma (visual field Mean Deviation (MD)≤‐12dB) and intraocular pressure(IOP)≤21mmHg on topical medications were prospectively studied(longitudinal data analysis).32 patients undergone phacoemulsification alone versus 23 patients undergoing combined phaco‐trabeculectomy. Main outcome measures: IOP(mmHg), visual acuity(VA)(logMAR), MD(dB), number of antiglaucoma medications needed postoperatively. Follow‐up 1 year.

Results The combined surgery provided more IOP reduction (‐5.76(‐7 to ‐4.5) mmHg) (p<0.001) and allowed the reduction of antiglaucoma medications postop by 2.2(2.7 to 1.8) (p<0.001). VA improvement was more by the time elapsed (p=0.014) and preoperative MD (p=0.006) and less by the presence of relative afferent pupillary defect(RAPD)(p<0.001). The MD change was related to the preoperative MD (p<0.001) while Cup‐Disc Ratio had a negative effect on postoperative MD change (p=0.001). The presence of RAPD reduced the MD change (p=0.052) while patients with pseudoexfoliation syndrome and women showed improvement in their MD postoperatively (p=0.038 and p=0.021, respectively).

Conclusion type of operation is the main predictive factor of the IOP change and number of antiglaucoma medication reduction. VA improvement is related to severe damage of the optic nerve and visual field change is related to the degree of glaucomatous damage of the optic nerve.
STARfloTM, a new suprachoroidal drainage implant for glaucoma: 3 months clinical results
Authors: POURJAVAN S , COLLIGNON N , DE GROOT V , GEENS P , MAGINNESS M , MARSHALL A , ROY C , ALVAREZ M
Published: August 2012

Purpose STARfloTM is a silicone implant for IOP reduction in POAG. STARfloTM is made with STAR® Biomaterial, a flexible tissue‐friendly, micro‐porous structure designed to reduce fibrotic response and maximize long‐term performance. The safety and performance endpoints of the study were; 1. Feasibility of STARfloTM device implantation; 2. Incidence of device and procedure related‐complication and unanticipated adverse device effects; 3. Reduction in IOP; 4. Reduction in number of glaucoma medications.

Methods 4 patients with advanced POAG and preop IOP>21 mmHg underwent STARfloTM implantation in suprachoroidal space. Outcome measures were IOP, biomicroscopy, ophthalmoscopy and the number of anti‐glaucomatous drugs on D1, W1, M1 and M3 postop.

Results Mean preop IOP was 37.0±8.4 mmHg and mean preop glaucoma medication was 2.5±1 intake/day. 1m postop (4 cases), mean IOP decreased to 21.8±9.7 mmHg (38.4% reduction/patient) and mean glaucoma medication decreased to 1.0±1.2 intake/day. At 3 m (3 cases), mean IOP was 25±11.3 mmHg (33.1% reduction/patient) and mean glaucoma medication was 1±1 intake/day. No adverse events were reported during or immediately postop and no device‐related serious adverse events were reported during follow‐up. Early complications were: transient hypotony for 2 cases, transient choroidal hemorrhage in 1 case, transient abnormal macula in 1 case. In 3 cases, bleb disappeared at month 1, and in 1 case it disappeared at month 3. 1 patient, with posttraumatic COAG, was dropped 4 m after implantation.

Conclusion Early results for STARflo met the safety and performance endpoints of study. STARflo reduces IOP in refractory glaucoma,

Commercial interest
Marginally controlled open angle glaucoma and cataract: sequential (1st phacoemulsification,2nd trabeculectomy) versus combined (phacotrabeculectomy) surgery
Authors: LIASKA A , ANDRIANOPOULOU K
Published: August 2012

Purpose glaucoma patients with borderline controlled intraocular pressure (IOP) may benefit from cataract surgery alone. However it is possible that these patients may need glaucoma surgery at some point in the future. Furthermore the risk of postoperative IOP spikes and the inconvenience of two operations (sequential) should be weighed against the complexity of the combined operation. The purpose of the study is to compare the results of phacotrabeculectomy with trabeculectomy in clear corneal incision pseudophacic eyes.

Methods retrospective study of 31 patients with visually significant cataract and open angle glaucoma with IOP 22‐25 mmHg on topical medications. The patients were assigned to either surgical treatment according to their glaucoma severity. 20 patients underwent combined phacotrabeculectomy (two‐sites) and 11 patients underwent sequential (1st phacoemulsification(temporal clear corneal incision with intraocular lens implantation), 2nd trabeculectomy). Antimetabolites and adjustable sutures were used in all glaucoma operations. IOP measurements were recorded. Follow up time was 6‐18 months (median 12 months).

Results the effect of type of surgical treatment on postoperative IOPs was not statistically significant. Combined phacotrabeculectomy resulted in higher IOPs by 0.97(95% Confidence Interval [‐1.6 3.59]) mmHg (p=0.47) versus sequential surgery.

Conclusion in patients with clinically significant cataract and glaucoma with borderline control of IOP the choice of combined (phacotrabeculectomy) versus sequential (1st phaco, 2nd trabeculectomy) surgery can be done according to the severity of glaucoma and based on surgeon’s preference and experience.
Local recurrence after uveal melanoma protontherapy: prognostic consequences
Authors: CAUJOLLE JP , PAOLI V , CHAMOREY E , MASCHI C , HANNOUN‐LEVI JM
Published: August 2012

Purpose To study the prognosis of the different types of uveal melanoma recurrences treated by proton beam therapy

Methods This retrospective study analyzed 61 cases of uveal melanoma local recurrence on a total of 1102 patients treated with protontherapy between June 1991 and December 2010. Survival rates have been determined by using Kaplan‐Meier curves. Prognostic factors have been evaluated by using Log‐rank test or Cox model.

Results Our local recurrence rate was 5.5%. These recurrences were divided into: 25 patients with marginal recurrences, 18 global recurrences, 12 far recurrences and 6 extra‐scleral extensions. 4 factors have been identified as statistically significant risk factor of local recurrence in univariate analysis: large tumoral diameter, weak tumoral volume, weak ratio of tumoral volume over eyeball volume and safety margin inferior to 1 mm. In the local recurrence free population, the overall survival rate was 59.8% at 15 years and the specific survival rate was 80.9% at 15 years. In the local recurrence population, the overall survival rate was 34.5% at 15 years and the specific survival rate was 55% at 15 years. Kaplan‐Meier survival curves have shown a better prognosis for marginal recurrences compared to the other recurrences.

Conclusion Survival rate of marginal recurrences is highly superior to the other recurrences. The type of recurrence is an important clinical prognostic value to know.
Lethal metastatic ciliary body melanoma without hepatic disease in a young girl
Authors: GRANGE JD , MONTEIRO S , BENTALEB Z
Published: August 2012

Purpose To illustrate a case report of rapid metastatic death due to a ciliary body melanoma in a a young female of 19 years of age, with no hepatic metastatic disease.

Methods A young algerian girl was send for conservative treatment for a ciliary body tumor of the left eye on the 19th of march 2012.This eye was blind, with a white cataract.Rubeosis iridis was present on the whole iris surface with total angle closure ,ocular pressure was 41 mm and US showed a temporal ciliary body tumor of 3.5 mm in height and 10 mm in diameter .

Results An enucleation was performed on March 20th , but the patient had to be hospitalized on the same afternoon in Intensive Care Unit for drainage of bilateral pleural effusion, purely inflammatory .Full Body CT Scan has shown brain secondary foci of 3 and 5 mm on both frontal lobes.A nodular lesion of 7 mm was also present on the Fowler lung lobe.The liver was not invaded but massive mesenteric necrotic lesions with peritoneal effusion were found. Surgical biopsy of the mesenteric lesions was done in the General Surgery Unit on March 22nd showing melanoma cells.In the same time the ocular pathologists diagnosis was an epithelioid ciliary body melanoma of 10x10 mm. On April 3rd a pleurodesis was created with pleural biopsies in the Thoracic Surgery Unit.Mesothelial pleural hyperplasia without malignancy sign was diagnosed.A chemotherapy with Muphoran has been advised by oncologists and begun soon after she returned in her country where she died at the end of May .

Conclusion Death by metastatic disease can also occur without detectable hepatic lesions by US or CT Scan in case of severe ciliary body melanoma.The mechanism of responsible mesenteric lesions for death in the hepatic vicinity has to be explained.
Fine needle aspiration biopsy in uveal melanoma : the Curie experience
Authors: DESJARDINS L , LEVY C , LUMBROSO‐LEROUIC L , CASSOUX N , SASTRE X , ASSELAIN B , PLANCHER C , COUTURIER J
Published: August 2012

Purpose In order to posssibly include uveal melanoma patients in a randomized trial on adjuvant therapy by Fotemustine we have started in 2009 to propose fine needle aspiration biopsy for genetic studies during clip or plaque positioning

Methods Biopsies were proposed to patients with uveal melanomas of more than 5 mm in thickness.we have used transcleral or transvitreal biopsies depending on the location of the tumor with 25 or 23 gauge needles. Histoacryl glue was used after transcleral biopsies and cryotherapy for transvitreal biopsies.Patients signed an inform consent

Results 108 biopsies were performed between January 2009 and april 2012; 6 patients had transient vitreal hemorrhages ( much more frequent with transvitreal p<0,0001))but no other side effects was observed. A sufficient quantity of DNA for CGH array was present in76% of cases, using whole genome amplification in 60% of cases. The quality of the specimen was strongly correlated with the presence of tumor cells’ p<0, 0001). 28, 7% of patients were classified as high genomic risk. No correlation was found between location and size of the tumor or any other clinical factor and the biopsy success rate

Conclusion fine needle aspiration biopsy is a safe procedure to allow genetic testing in uveal melanoma patients
Importance of visual evoked potential in amblyopic children
Authors: HALFELD FURTADO DE MENDONCA R , ABBRUZZESE S , BAGOLINI B , NOFRONI I , FERREIRA EL
Published: August 2012

Purpose To compare responses to VEP of amblyopic and sound eyes in amblyopic children.

Methods Observational descriptive study of 65 amblyopic children (ages between 20‐162 months) with pattern reversal VEPs elicited by checkerboard stimuli with large (120’) medium (42’) and small (12’) checks.

Results No statistically significant difference was revealed concerning P1 amplitude and latencies for any check sizes between the amblyopic and sound eye of amblyopic children.

Conclusion VEP is a very important tool to understand the complex amblyopic mechanism. Although the superior VA of the sound eye, the VEP alterations demonstrate the functional abnormality of the eye considered “good”. More studies are necessary to explain why the sound eye in amblyopic children cannot be considered completely normal therefore, special attention should be paid to amblyopic treatment, as patching can have a negative effect on the sound eye.
Evaluation of a new technique to evaluate the visual pursuit in infants
Authors: MONTEIRO K , CHARLIER J , DEFOORT‐DHELLEMMES S
Published: August 2012

Purpose This study presents a new technique for recording visual pursuit and its evaluation. In infants, visual acuity is usually estimated using behavioral methods. Nowadays, an objective response can be recorded using eye trackers based on the corneal reflex and pupil positions. However, these systems have limitations, such as large eye eccentricity and parasite reflections on tears or eyeglasses. To avoid these constraints, a new technique has been developed and evaluated.

Methods The system is composed of a stimulation monitor equipped with a near infra‐red light source and a video camera. A real‐time analysis of the video identifies the head position, using a reflective dot placed between the patient’s eyes. The gaze orientation is obtained from the relative position of the reflective dot and the eye pupils. Clinical tests were carried out on 90 infants (3 months to 4 years). Gabor type stimuli moving along the horizontal axis were presented while head and eye movements were recorded.

Results Visual pursuit was recorded in 84 infants, some of them with nystagmus or large eye deviation. The visual tracking patterns matched with the literature, i.e. saccadic for the youngest ages and smooth in older normal children.

Conclusion Results show that the new technique is robust and efficient for recording infants’ visual pursuit under clinical conditions. Further tests are planned to evaluate if visual acuity estimation agrees with clinical exams.

Commercial interest
Neuroprotective and regenerative effect of neurotrophin‐4 on neuronal degeneration induced by advanced glycation end‐products in adult rat retinas
Authors: BIKBOVA G , OSHITARI T , YAMAMOTO S
Published: August 2012

Purpose To determine the effect of AGEs with or without NT‐4 on neuronal cell death and regeneration in isolated rat retinas.

Methods Retinal explants of 4 adult SD rats were three‐dimensionally cultured in collagen gel and were incubated either in; 1) serum free control culture media, 2) 10 μg/ml glucose‐AGE‐BSA media, 3) 10 μg/ml glycolaldehyde‐AGE‐BSA media, 4) 10 μg/ml glyceraldehyde‐AGE‐BSA media, 5) glucose‐AGE+100ng/ml NT‐4 media, 6) glycol‐AGE+100ng/ml NT‐4 media, or 7) glycer‐AGE+100 ng/ml NT‐4 supplemented culture media. After 7 days, the number of regenerating neurites from the explants was counted under a phase‐contrast microscope. After counting, retinal explants were fixed, cryosectioned, and stained by TUNEL and DAPI. The ratio of TUNEL‐positive cells to the number of DAPI‐staining nuclei in the ganglion cell layer was calculated. Statistical analysis was performed by one‐way ANOVA.

Results In retinas incubated with AGEs (glucose‐AGE, glycol‐AGE, and glycer‐AGE), the numbers of regenerating neurites were fewer than in retinas without AGE (P=0.0033, P=0.0044, and P=0.0238, respectively) and the numbers of TUNEL‐positive cells were higher than in control media (P<0.0001, respectively). NT‐4 supplementation increased, the numbers of regenerating neuritis (P<0.0001) and the numbers of TUNEL‐positives cells were significantly lower than those in glucose‐AGE without NT‐4 (P<0.001) in glycol‐AGE without NT‐4 (P=0.005) and in glycer‐AGE without NT‐4 (P=0.0003).

Conclusion AGEs induce neuronal cell death and impede neurite regeneration in adult rat retinas. NT‐4 significantly enhances neuronal survival and regeneration in retinas exposed to AGEs.
Generating human retinal ganglion cells from human induced pluripotent cells in feeder and feeder‐free conditions
Authors: ALSHAMEKH S , HERTZ J , DEROSA B , UDDIN S , PATEL R , SALERO E , DYKXHOORN D , GOLDBERG JL
Published: August 2012

Purpose Glaucoma, and other optic neuropathies, results in the loss of retinal ganglion cells (RGCs) and vision dysfunction. Therefore, cell replacement therapy may offer promising treatments to protect the degenerating retina and potentially restore vision function. Although significant progress has been made to generate photoreceptors from stem cells, there has been little advancement in efficiently generating RGCs. Therefore, we have been investigating the optimal conditions for differentiating RGCs from stem cells for cell replacement therapy.

Methods Human induced pluripotent stem cells (iPSCs) were maintained and expanded on feeder layers using previously published conditions. During embryoid body formation, genes and proteins were tested for effects on increasing RGC differentiation efficiency. Differentiated RGCs were identified and quantified using RGC‐specific markers including Brn3. Feeder‐free conditions were examined for functional equivalence.

Results iPSCs that express stem cell‐specific markers were passaged in proliferative conditions and differentiated into RGCs in vitro. Feeder‐free cell culture conditions allowed iPSC maintenance without the presence of mouse immunogenicity. iPSCs were found to respond to pro‐RGC differentiation signals in similar fashion to rodent embryonic retinal progenitors.

Conclusion These findings will provide valuable insight in our understanding of RGC differentiation and will pave the way to cure retinal diseases. The transplantation of these cells in vivo will elucidate the integration potential of these cells in degenerating retina.
The use of propranolol in the treatment of periocular infantile hemangiomas
Authors: BUIJSROGGE M , CLAERHOUT I , DELBEKE P , WALRAEDT S , DECOCK C
Published: August 2012

Purpose Infantile capillary hemangiomas (IH) are the most common tumours of the eyelid and orbit in infants. Despite their self‐limited course, IH can impair visual function. Recently, the use of propranolol was found to reduce the size of IH. We will present our own case series of patients with periocular IH treated with propranolol to illustrate these findings.

Methods We conducted a retrospective study on 10 children with IH treated with propranolol. After exclusion of any contra‐indication, propranolol was initiated at a dose of 1 mg/kg/d. After 10‐14 days, patients were checked again for side‐effects. If these were absent, propranolol was increased to 2 mg/kg/d. Further follow‐up consists of monthly clinical and photographical evaluations of the IH, monitoring of treatment compliance and tolerance. Success of treatment is defined as stopping growth or reducing size. The response to treatment was rated by 3 blinded, independent observers.

Results The age range at start of treatment with propranolol was between 2 and 19 months (mean 6,8 months). The mean age at stopping propranolol was 14,4 months. The mean duration of treatment was 7,6 months and only 1 patient had to stop treatment because of side effects. Two patients (20%) had a rebound after temporary stop of propranolol. The success rate in our case serie was 100%. Half of the group had excellent results, 30% had a good response and 20% had a fair response. We also obtained objective measures of astigmatism and anisometropia in 6 patients. We report a reduction in anisometropic astigmatism in 5 of these 6 patients.

Conclusion These data support the current perception that propranolol is a highly effective first line treatment for IH with very limited and mild side effects.
AICAR induces effectively autophagy clearance in ARPE‐19 cells
Authors: KAARNIRANTA K , VIIRI J , HYTTINEN J , SALMINEN A
Published: August 2012

Purpose The ubiquitin‐proteasome pathway and lysosomal pathway including autophagy are the master clearance systems in cells. The p62/sequestosome 1 (p62) and LC3 have been observed to be key players linking the proteasomal and lysosomal clearance systems. In this study, crosstalk of proteasomes and autophagy was examined.

Methods Effect of autophagy activator (AICAR) and inhibitor (bafilomycin) on protein aggregation and autophagy markers were studied in the ARPE‐19 cells treated with proteasome inhibitor (MG‐132, 5µM) with or without AICAR (2mM) or bafilomycin (50nM) for 24h hours. Autophagy gene activation was studied by cDNA PCR array. The protein levels of LC3 were evaluated by western blotting. The localization and movement of p62 and LC3 were analyzed by live confocal microscopy. Cellular organelles were visualized by transmission electron microscopy.

Results MG‐132 clearly increased perinuclear protein aggregation, while AICAR robustly decreased the amount of aggregates together with LC3 activation. AICAR upregulates the most important autophagy genes. We show that p62 and LC3 colocalizes with the protein aggregates that all are finally degraded in autophagy.

Conclusion Autophagy is effective clearance machine in RPE cells that might be a novel therapy target to prevent cell degeneration.
The p62/sequestosome 1 binds irreversibly to protein aggregates prior to autophagy clearance in ARPE‐19 cells
Authors: VIIRI J , HYTTINEN J , SALMINEN A , KAARNIRANTA K
Published: August 2012

Purpose The pathogenesis of AMD involves impaired protein degradation in RPE cells. The ubiquitin‐proteasome pathway and the lysosomal pathway including autophagy are the major proteolytic systems in eukaryotic cells. Recently, p62/sequestosome 1 (p62) has been shown to be a key player linking the proteasomal and lysosomal clearance systems. In this study, expression and trafficking of p62 was examined.

Methods To study the effect of autophagy activator (AICAR) and inhibitor (bafilomycin) on p62 expression levels, the ARPE‐19 cells were treated with proteasome inhibitor (MG‐132, 5µM) with or without AICAR (2mM) or bafilomycin (50nM) for 24h hours. The protein levels of p62 were evaluated by western blotting. The localization and movement of p62 were analyzed by live confocal microscopy.

Results MG‐132 increased the p62 protein levels, while AICAR robustly decreased the p62 levels. When autophagy was inhibited with bafilomycin the p62 was highly accumulated. We show that p62 binds irreversibly to protein aggregates that are finally degraded in autophagy.

Conclusion The p62/sequestosome 1 function as a linker protein between proteasomes and autophagy and can be used as a autophagy flux marker. Autophagy is effective clearance machine that may be disturbed in aged RPE cells.
The VIEW Studies: clinical results in wet AMD
Authors: WEBER M
Published: August 2012

The study design, treatment schedule and the results of the clinical trials VIEW 1 and 2 are shown, including the primary and secondary endpoints. All VEGF Trap‐Eye treatment regimens were non‐inferior to monthly ranibizumab treatment, and achieved numerically similar outcomes on all endpoints assessed. The results of the follow‐up phase at week 96 are presented including safety and efficacy data.
Response of retinal blood flow to systemic hyperoxia as measured with dual‐beam bidirectional Doppler Fourier‐domain optical coherence tomography
Authors: PALKOVITS S , WERKMEISTER R , TOLD R , GRÖSCHEL M , LEITGEB R , GARHÖFER G , SCHMETTERER L
Published: August 2012

Purpose Much effort was directed towards the quantification of retinal blood flow in the past decades. In the recent years, optical coherence tomography (OCT) based systems were introduced to measure retinal perfusion. The current study compares a new technique, dual beam bidirectional Doppler Fourier domain OCT (FD‐OCT), with laser Doppler velocimeter (LDV), while breathing ambient air and pure oxygen.

Methods 10 healthy volunteers were included into the present study and two study days were scheduled. On one study day assessment of the effect of 100% O2 breathing on retinal blood velocities was performed using FD‐OCT. LDV was used to investigate retinal blood velocities on the other study day. In addition to velocity measurements retinal vessel diameters were assessed with Dynamic Vessel Analyzer (DVA, Imedos, Germany). Baseline data as well as hyperoxia data were compared between each study day.

Results Reduced vessel diameters, velocities and blood flow were found while breathing 100% O2 compared to baseline. Our findings showed a high correlation between retinal blood velocities obtained with the OCT system and the LDV during baseline and under hyperoxia (p<0.01 each). However, velocities measured with the OCT were slightly higher.

Conclusion Good correlation was found between dual‐beam bidirectional Doppler FD‐OCT and LDV data. Dual‐beam bidirectional Doppler FD‐OCT is a promising approach for studying retinal blood flow in vivo.
Dexamethasone drug delivery system (Ozurdex) for the treatment of refractory diabetic macular oedema: retrospective case series analysis
Authors: AKNIN I , MELKI L
Published: August 2012

Purpose The purpose of this study is to report the clinical outcome of the treatment of DME patients with the Dexamethasone Drug Delivery System (Ozurdex) in clinical practice.

Methods This retrospective case series study included 25 consecutive patients (25 eyes) with refractory DME. This preliminary report includes 10 patients who completed a 12 months follow‐up. VA (EDTRS), CRT (OCT) and IOP were assessed at baseline, 7 days, and 1, 6 and 12 months after Ozurdex injection. If necessary, a second implant was injected at 6 and/or 12 month.

Results The mean duration of diabetes at baseline was 18.6 years with a mean HbA1c level of 8.97. At baseline the mean VA was 52 letters, mean CRT 467µm and mean IOP 15.9 mmHg. At day 7, the mean VA increased to 62.22 letters (+ 10.22 letters) and the mean CRT decreased to 290.25µm with a mean IOP level of 16.66 mmHg. At month 1: mean VA was maintained to 58.66 letters (+ 6.66 letters) and the CRT continued to decrease to 201µm.The mean IOP slightly increased to 17.83 mmHg (we had 1 case at 24 mmHg) At month 6: mean visual acuity continued to increase to 64.33 letters (+12.33 letters gain). The mean CRT was 281µm with an IOP level of 15.16 mmHg. At month 12: mean visual acuity was maintained to 65.41 letters (2‐line gain: + 13.41 letters), mean retinal thickness and IOP level were normal (200µm and 16.81 mmHg respectively). At month 12: 5 patients (50%) had an improvement of more than 15 letters. 50% of the patients underwent a second injection, and 33% of them

Conclusion The present clinical study suggests that intravitreal injection of the dexamethasone drug delivery system (Ozurdex) seems to be effective and well tolerated in eyes with refractory DME
Retinal vascular reactivity over extended vessel segments
Authors: KALITZEOS A , SUMMERS RJ , HEITMAR R
Published: August 2012

Purpose To assess the impact of vessel segment length when analysing retinal vessel responses to flicker light provocation in healthy individuals.

Methods 12 healthy individuals (mean age 30±6) underwent digital sphygmomanometry (UA‐767, A&D Instruments, UK), non‐contact tonometry (Keeler Pulsair, UK) and dynamic retinal diameter assessment using the retinal vessel analyser (Imedos Systems, Germany) in order to evaluate the influence of segment length on flicker light induced dilation of retinal arterioles and venules. Up to seven segments of each superior artery and vein, were extracted off‐line from video recordings of each subject within a minimum distance of 1 disc diameter (DD) from the rim of the optic nerve head and up to a maximum of 4 DD away from the rim.

Results Retinal arteriolar and venular dilation amplitude were independent of segment length, blood pressure and intraocular pressure.

Conclusion Independence of segment length is essential as retinal vessel anatomy is highly variable, some individuals having numerous vessel crossings and bifurcations making it difficult to measure long vessel segments.
Infection and inflammation in Boston Type 1 KPro
Authors: ETXEBARRIA J , ORIVE A , SANTAMARIA A , FEIJOO R
Published: August 2012

Purpose We show possible risk factors for extrusion or endophthalmitis , significance of different clinical features, how to approach them clinically and surgically in order to try to obtain the most successful results in patients who underwent Boston KPro type I surgery.

Methods Review of clinical experience through the last 6½ years dealing with Boston KPro type I surgeries and subsequent possible complications such as melting, thinning, extrusion and endophthalmitis.

Results The main risk factor for KPro failure is inflammation level of the ocular surface. The origin of this inflammation can be diverse: blepharitis, mechanical, immunological. Many inflammatory molecules, through different pathways, can lead to an increase of many metalloproteinases which are involved in the digestion of corneal collagen, producing melting, cornea thinning or even KPro extrusion. Infectious keratitis or endophthalmitis are other dramatic possible complications in KPro patients that can also be associated to collagenolisi

Conclusion Control of ocular surface inflammation is crucial to succeed in the postop of KPro surgeries. In order to achieve this point, management of clinical signs, use of different topical and systemic drugs, and some tricky surgeries should be learned. In case of endophthalmitis, very early surgery consisting of removal of KPro, pars plana vitrectomy and keratoplasty is mandatory.
Oculoplastic complications of OOKP surgery
Authors: AVADHANAM V , HAWKES G , BRITTAIN P , HEROLD J , THORP S , LIU C
Published: August 2012

Purpose To report the incidence, types and management of oculoplastic complications following OOKP surgery.

Methods A retrospective review of case records of 60 patients who underwent OOKP surgery was performed between November 1996 and March 2012. Mucous membrane, eyelid and cosmetic complications were studied following each stage in the two stage OOKP procedure.

Results Patients age ranged from 19 to 95 years and the follow up duration varied from 6 months to 15 years. The commonest diagnosis was Stevens‐Johnson syndrome followed by chemical or thermal burns and mucous membrane pemphigoid. Forty nine or 82% of these patients had some form of oculoplastic complication. After the Stage 1, 27% of these patients had mucous membrane complications and 15% had eyelid complications. Following the Stage 2, 68% of these patients had mucous membrane complications and 53% had eyelid complications Three patients wore cosmetic shells and all of them had shell fitting problems. Most of the complications were successfully managed with appropriate surgical procedures.

Conclusion Oculoplastic complications are the most common complications after the OOKP surgery. They are most frequently noted following the Stage 2 procedure. The outcome is generally favorable with timely recognition and management and they do not usually have an adverse affect over visual acuity.
Psychological factors and complications in OOKP assessment and surgery
Authors: BUSUTTIL A , HEROLD J , LIU C
Published: August 2012

Purpose To highlight how psychological factors can complicate OOKP assessment , surgical outcome and adaptation to living with OOKP and to demonstrate how these issues can be addressed.

Methods Single case studies will be used to illustrate the clinical presentation of psychological issues and how these may have impacted on medical progress and adjustment post surgery.

Results Cases will illustrate how a previous psychological trauma history, mood disorder and identity issues can impact on physical, psychological and social adjustment to OOKP. The case studies will also illustrate interventions which addressed these.

Conclusion For some patients ,the identification of psychological problems and their appropriate management is important for succesful outcome and adaptation in OOKP surgery.