bluuebunny/crossref_metadata_2025 huggingface dataset:
Intravitreal anti‐VEGF in submacular hemorrhage due to age related macular degeneration
Authors: DESSERRE J , LABALETTE P
Published: August 2014

Purpose To evaluate efficacy and prognostic factors of intravitreal anti‐VEGF for large submacular hemorrhage (HSM) secondary to age‐related macular degeneration (AMD).

Methods Eighteen eyes of 18 patients with HSM neovascular AMD were reviewed. HSM had to respect a diameter greater than three papillary disk diameters and with fovea participation. Visual acuity was considered at diagnosed and when best final visual acuity was achieved. HSM outcomes were measured by SD‐OCT. Statistical analysis was used to evaluate association between visual acuity and different outcomes: macular status of fellow eye, hemorrhagic surface, hemorrhage localization, central foveal thickness, highest macular thickness and macular volume.

Results Mean duration of symptoms was 25.94 +/‐ 32 days. Mean anti‐VEGF injection was 3.31 +/‐ 0.3. Mean hemorrhagic surface was 8.77 +/‐ 6.52 disc areas. 62 % patients presented their first exudative episode. The mean logMAR visual acuity improved from 1.5 +/‐ 0.52 to 1.0 +/‐ 0.40 at final examination (p=0.04). A gain of three EDTRS lines or more was found in 50% patients. No association was evident between opposite side status, hemorrhagic surface and initial central fovea thickness with final visual acuity. Although an association between highest macular thickness, macular volume (p 0.05) and final visual acuity was significant. Patients with predominant sub‐retinal pigment epithelial hemorrhage seemed to have a worst visual prognosis.

Conclusion Anti‐VEGF therapy is a useful treatment for large HSM. In our study, highest macular thickness and macular volume at diagnosis seem more predictive than central fovea thickness or hemorrhagic surface. Factor prognosis need to be clearly identify to select patients for surgical procedures.
Treatment of neovascular AMD by Aflibercept (Eylea) with proreactive protocol
Authors: GONZALEZ C
Published: August 2014

Purpose To evaluate the functional, anatomical, vascular flow, effects of intravitreal Aflibercept injections(IVT) for subretinal neovascularisation complicating AMD, done with Proreactive protocol, and the recurrences frequency at 1 year follow‐up

Methods 42 eyes of 38 patients, 12 men, 26 women, with subretinal neovascularisation complicating AMD. 38 eyes were switch cases, 4 naïve cases. Patients received intravitreous Eylea, 3 times, every 4 weeks in an inductive treatment. The next injections depended on the follow‐up results, and were done by series of 3 IVT, IVT done every 1 ½ months. First exam, 2 months, and then 3 months’ interval follow‐up exam included ETDRS visual acuity (VA), complete ophthalmic examination, optical coherence tomography (OCT), fluorescein and infracyanine (ICG) angiography.VA and OCT were done before each IVT. We want to evaluate the incidence of this protocol on the functional results and frequency of recurrences so on the number of IVT needed

Results VA improved in 44% cases, more than 10 letters in 22% cases. Diffuse edema was 30% reduced in 88% , pigment epithelial detachment was flattened and less dense in all cases, by OCT. Angiographic leakage reduced about 70% in 65% cases, 30% in 96% cases. At ICG, vascular flow, vessel’s diameter were 2/3 time less in 68% cases,1/3 in 97% cases. Most of patients had good functional, anatomical, vascular flow, results, with less IVT needed. Inductive treatment was sufficient in 12 cases, needed added IVT in 30 cases. This protocol was compared, discussed

Conclusion The results,improved visual function, reduction of exudation, leakage, low neovascularisation’s flow at OCT , AF and ICG, less recurrences, suggest Proreactive Eylea protocol seems effective, less restrictive and appears attractive
The functional effects and expression of HGF and FGF in the choroid
Authors: STEWART EA , AMOAKU WM
Published: August 2014

Purpose Age‐related macular degeneration is the most common cause of irreversible visual loss in the increasingly ageing population of the western world. Most current treatments focus on sequestering excess vascular endothelial growth factor (VEGF) produced in response to inflammation and ischaemia. However, compensation by other angiogenic growth factors such as hepatocyte growth factor (HGF) and fibroblast growth factor (FGF) may occur.

Methods Expression of HGF and FGF and their receptors MET and FGFR2 was investigated in vivo and in vitro in choroidal endothelial cells (CEC) using immunostaining, western blotting and ELISA. The in vitro response of CEC to these factors was assessed using proliferation and angiogenesis assays. Real time PCR was used to quantify signalling responses through gene expression of key signalling molecules such as HIF and expression of VEGF.

Results Expression of HGF, FGF and their receptors was found in human choroid and cultured CEC. Both growth factors increased proliferation and angiogenesis independent of, and additive with VEGF. VEGF and HIF gene expression were altered dependent on growth factor concentration and time.

Conclusion Although much research and treatment focuses on VEGF, other growth factors which may compensate for the loss of VEGF signalling have significant stimulatory effects on angiogenesis. This study supports recent clinical advances into combination therapies.

Commercial interest
Risk of ocular complications in persistent non‐infectious non‐anterior uveitis
Authors: DICK A , TUNDIA N , SKUP M , SORG R , ZHAO C , BAO Y , CHAO J
Published: August 2014

Purpose To assess risk of developing ocular complications in privately insured US patients with persistent non‐anterior NIU compared to matched controls without uveitis.

Methods Adults 18–64 years old with ≥2 NIU ICD‐9‐CM claims for intermediate‐, posterior‐ or pan‐NIU were identified (OptumHealth, 01/01/1998–31/03/2012), and those with ≥90 days of corticosteroids, immunosuppressants, and/or biologics use were defined as persistent cases. Cases were matched 1:1 by sex, age, region, company, employment status, and index date to controls. Risks of developing ocular complications were compared using unadjusted Kaplan‐Meier survival (risk of and time to complications) and adjusted Cox regression (hazard ratios) analyses.

Results During the follow‐up period, persistent cases (N=302) had significantly higher risk of any ocular complication vs their matched controls (P<.001); the 1‐, 5‐ and 10‐year risks were 55% vs 5%, 83% vs 27%, and 88% vs 49%, respectively. Five‐year risks of specific complications for cases vs controls were glaucoma (31% vs 10%), cataract (57% vs 14%), visual disturbance (41% vs 9%), blindness/low vision (4% vs 2%), retinal detachment (13% vs 1%), and retinal disorder (42% vs 3%). Adjusted analysis showed persistent cases had hazard rates that were 8.9, 8.1, 6.2, and 4.2 times higher than controls for any complication, visual disturbance, cataract, and glaucoma, respectively.

Conclusion Patients with persistent non‐anterior NIU are at high risk of ocular complications, which suggests high unmet need for an optimal treatment.

Commercial interest
Bilateral ocular involvement in a patient with tertiary syphilis
Authors: ZOZOLOU M , MINAKAKIS P , KANELLAS D , XIROU T , KABANAROU S , VAIKOUSIS E
Published: August 2014

Purpose To report a case of a 46‐year‐old man with bilateral neuroretinitis due to tertiary syphilis.

Methods The patient presented at the clinic with a history of blurred vision. He was agitated and was looking unwell. Snellen Visual acuity (VA) was 0.2 in the right eye and 0.1 in the left eye. Pupillary reflexes to light were sluggish but normally reactive to accommodation. Fundoscopy showed bilateral optic disc oedema and fluorescein angiography revealed active neuroretinitis. Visual fields (VF) were abnormal in both eyes. Laboratory blood tests, cardiological investigations and a brain MRI were performed. Mantoux test was negative and IV treatment with corticosteroids was initiated.

Results Treatment with steroids was discontinued due to the appearance of a maculopapular rash on the head and neck. Laboratory results showed: RPR (Rapid Plasma Reagin)/FTA: positive, TPPA of serum and CSF (IgG, IgM): positive. Virological tests were negative. Based on these findings the diagnosis of neurosyphilis was made. Cardiological investigation was normal and brain MRI did not show any major abnormalities. Patient was started on IV crystalline penicillin, 3‐4 million units q 4h for two weeks. Three months after treatment VA was 0.6 in the right eye and 0.4 in the left. There was an improvement on the VF mainly in the right eye. Electro‐encephalogram showed no significant pathology. ISCEV standard full field and pattern electroretinography were affected bilaterally.

Conclusion Bilateral neuroretinitis due to tertiary syphilis affects vision and complete visual recovery may not occur despite adequate treatment.
Reactivation of oxoplasmic retinochoroiditis after macula hole surgery
Authors: HALFELD FURTADO DE MENDONCA R , DE OLIVEIRA MAIA JR O
Published: August 2014

Purpose To describe a very interesting case of reactivation of ocular toxoplasmosis after macula hole surgery. Setting : Toxoplasmic retinochoroiditis is the most frequently cause of posterior uveitis worldwide and reactivation is unpredictable.

Methods A 53 year old high myopic man complained of blurred vision in his left eye over the past 3 months. He underwent cataract surgery with IOL in both eyes one year ago with success. Visual acuity in the right eye was 20/20 and in the left eye 20/400. The intraocular pressure was 12 mmHg in both eyes. Fundus examination of the right eye was normal. Fundus examination of the left eye showed a macular hole and a small inactive toxoplasmosis scar.

Results The patient underwent vitrectomy to relieve traction on the edge of the hole. At 20‐days follow‐up, the visual acuity in the left eye was 20/100. Fundus examination showed a complete resolution of the macular hole. Two months later, the patient had a reactivation of the toxoplasmic retinochoroiditis and the visual acuity dropped to counting fingers at 2 meters. After a specific treatment for Toxoplasmosis, the visual acuity improved to 20/80 (two months later).

Conclusion Toxoplasmosis reactivation may develop after vitrectomy. More studies are necessary to confirm if, in the presence of preoperative toxoplasmic chorioretinitis scars, the prophylactic treatment with antiparasitic drugs is necessary.
Ocular manifestations in Korean patients with transbronchial lung biopsy‐proven sarcoidosis
Authors: SHIN J , YUNG Y
Published: August 2014

Purpose To evaluate the characteristic ocular signs and systemic examination findings in patients with transbronchial lung biopsy (TBLB)‐proven sarcoidosis.

Methods A total of 28 patients with TBLB‐proven sarcoidosis were evaluated between January 2011 and December 2012. The medical records of patients were retrospectively reviewed. We evaluated the following five characteristic ocular signs that are suggestive for the diagnosis of sarcoidosis: (1) mutton‐fat keratic precipitates and iris nodules; (2) nodules at the trabecular meshwork and tent‐shaped peripheral anterior synechia; (3) snowball or string‐of‐pearls vitreous opacities; (4) nodular periphlebitis; (5) multiple chorioretinal lesions. The results of systemic examination, including serum angiotensin converting enzyme (ACE) assay, chest radiography or computed tomography of the chest, pulmonary function tests (PFT), tuberculin skin test and bronchoalveolar lavage (BAL), were considered for each patient.

Results Eighteen patients (64.2%) showed ocular signs, which are suggestive of ocular sarcoidosis. Thirteen (72.2%) of these 18 patients presented with ocular signs as the initial manifestation of the disease. The typical findings of chest CT, such as bilateral hilar lymphadenopathy (BHL), were observed in all of the 28 patients.

Conclusion It can be suggested that intraocular lesions could be the sole clinical manifestation of the disease. Therefore, it is important to perform pulmonary examination including chest CT in patients with suspicious ocular sarcoidosis.
Bilateral multifocal chorioretinitis and optic neuritis due to epstein‐barr virus; a case report.
Authors: CHATZIRALLI I , PARIKAKIS E , PEPONIS V , DRAKOS E , MITROPOULOS P
Published: August 2014

Purpose Only few cases of Epstein‐Barr virus (EBV) involving the retina or the optic nerve have been reported. Our purpose was to report a case of bilateral chorioretinitis and optic neuritis due to EBV.

Methods A 67‐year‐old man with no previous ocular history presented with decreased vision in both eyes since two months. The patient underwent a thorough ophthalmological examination, including visual acuity measurement by means of Snellen charts, slit‐lamp examination, intraocular pressure (IOP) measurement and dilated fundoscopy. His past medical history included EBV encephalopathy, which was confirmed serologically, few months before.

Results At presentation, his best corrected visual acuity (BCVA) was 6/60 in the right eye and hand movement in the left eye. The anterior segment was totally normal and IOP was normal in both eyes as well. Dilated fundoscopy revealed multiple, well‐demarcated, gray to white areas of retinal atrophy involving predominantly the periphery in the right eye and the macula in the left eye. Of note, all lesions were on the pathway of retinal vessels. Bilateral chorioretinitis and optic neuritis were confirmed by fluorescein angiography as well as electrophysiological tests and presumed to be due to EBV.

Conclusion It is very important to include EBV in the differential diagnosis of chorioretinal atrophic lesions. Clinicians should be aware of ocular manifestations of EBV, in order to suggest ophthalmological examination and start treatment promptly before irreversible damage of the optic nerve or retina.
Rare ocular involvement due to leukocidin “panton valentine” (pvl) positive staphylococcus aureus after bacterial endocarditis
Authors: ZOZOLOU M , MINAKAKIS P , PASCHALIDIS T , XIROU T , KABANAROU S , VAIKOUSIS E
Published: August 2014

Purpose To present an unusual case of a 38‐year‐old man with pituitary apoplexy, bacterial endocarditis, and chorioretinitis due to leukocidin “PVL” positive staphylococcus aureus, not reported in the current literature.

Methods He presented with a history of sudden loss of vision, headache and high fever. Visual acuity (VA) was Hand Movements in both eyes with sluggish pupillary reflexes. Fundoscopy revealed bilateral yellowish focal retinal lesions and Roth’s spots in right eye, indicative of active chorioretinitis. Fluorescein angiography (FA) showed active chorioretinal lesions. Visual fields and OCT were normal. Brain MRI showed a pituitary adenoma. The diagnosis of pituitary apoplexy was made based on clinical history, systemic findings and MRI imaging. He was treated with high doses of IV steroids. Snellen Visual acuity (VA) was improved to 0.8 in the right eye and 0.9 in the left eye. Three days later he presented Osler΄s nodes and septic emboli on palms and soles, characteristics of bacterial endocarditis. Blood culture showed leukocidin “PVL” positive staphylococcus aureus. Transesophageal echocardiogram demonstrated prolapse and degenerative alterations of the mitral valve. A quadruple IV antibiotic treatment was initiated for eight weeks. An operation to remove the pituitary adenoma in two months was also scheduled.

Results One year later his VA was 10/10 bilaterally. FA showed inactive chorioretinal scars. ISCEV standard full field ERG was affected bilaterally.

Conclusion Ocular complications may follow pituitary apoplexy and bacterial endocarditis due to “PVL” (+) Staphylococcus aureus. Early diagnosis is important for an effective treatment.
Efficacy of dexamethasone intravitreal implants in macular oedema excluding venous occlusions : results about 80 patients
Authors: DEGOUMOIS A , AKESBI J , LAURENS C , RODALLEC T , ADAM R , BLUMEN‐OHANA E , LAPLACE O , VIREVIALLE C , LE DÛ B , GUYADER V , NORDMANN JP
Published: August 2014

Purpose The dexamethasone intravitreal implant has shown efficacy in the treatment of macular edema (ME) of non‐infectious uveitis and retinal venous occlusions. The aim was to evaluate the efficacy of this implant in the treatment of other diffuse macular edemas with an inflammatory mechanism.

Methods Retrospective cohort study over 2 years : from January 2012 to December 2013, including all patients who received at least one injection of intravitreal dexamethasone implant, excluding venous occlusions and non‐infectious uveitis. The primary endpoint was the change in visual acuity.

Results 80 patients were included. The indications of treatment were : diabetic ME when anti‐VEGF were ineffective (53%), ME after retinal detachment(RD)(22%), ME of Irvine Gass syndrome(16%), ME after endophtalmitis(4%), macular telangiectasia(4%), ME of retinitis pigmentosa(1%). The mean ETDRS visual acuity was 53.7 letters before injection, 62.3 letters after injection (p<0.001). The average gain in visual acuity was 6.7 letters [4.5;8.8](p<0.001) in patients treated for diabetic ME, 9.6 letters[6.1;13.1] (p<0.001) for ME after RD, and 15.2 letters[10.2;20.2] (p<0.001) for Irvine Gass syndrome. The mean duration of efficiency was 4.6 months, with a median of 3.8 months.

Conclusion The intravitreal implant of dexamethasone appears to be an effective second‐line treatment even in patients with diabetic ME after failure of anti‐VEGF. It is also effective and well tolerated in patients with ME after RD, and Irvine Gass syndrome.
Clinical review of rhegmatogenous retinal detachment in Korea – Does seasonal variation exist in rhegmatogenous retinal detachment?
Authors: JIN H , LIM HS , LEE KH
Published: August 2014

Purpose We investigated demographic and clinical features including seasonal variation of rhegmatogenous retinal detachment in Suwon, South Korea.

Methods We reviewed medical records of 778 patients who were diagnosed with rhegmatogenous retinal detachment at Ajou university hospital located in Suwon City (Gyeuonggi‐do, South Korea) from February 1995 to December 2013. Incidence of rhegmatogenous retinal detachment was counted by months and seasons. Demographic and clinical features were also analyzed.

Results Total 778 eyes of 778 patients (778 patients; 418 men and 360 women; the mean age, 46.6 ± 17.3 years; range, 10‐85 years) were included in the study. 86.1% (670 eyes) of eyes were phakic and high myopic eyes accounted for 11.6% (90 eyes) of the cases. The cases with single retinal break were 47.9% (373 eyes) and the average count of retinal break was 1.46. 65.8% (512 eyes) of the cases were treated successfully with sclera buckling. Incidence of retinal detachment was not different according to months (p=0.385) and seasons (p=0.090). Comparing the results of warm seasons (spring and summer) and cold seasons (autumn and winter), incidence of rhegmatogenous retinal detachment did not differ (p=0.071).

Conclusion Unlike previous reports in Japan, Middle East and Europe, our study has no correlation with seasons. Previous studies suggested the higher incidence of rhegmatogenous retinal detachment in warm seasons is due to ambient temperature and increased outdoor activity, but summer in Korea is highly humid and hot. Also, it includes long rainy season, so it is not a good season for outdoor activity as other regions. These features may influence the result of our study.
Significant visual improvement after spontaneous resolution of longstanding macular detachment due to optic disc pit
Authors: PARIKAKIS E , CHATZIRALLI I , STRATOS E , PEPONIS V , KARAGIANNIS D , TSIOTRA V , MITROPOULOS P
Published: August 2014

Purpose To report a case of spontaneous resolution of a longstanding serous macular detachment associated with an optic disc pit, leading to significant visual improvement.

Methods A 63‐year‐old female presented with blurred vision and micropsia in her left eye since six months. Her best‐corrected visual acuity was 6/24 in the left eye and fundoscopy revealed serous macular detachment associated with optic disc pit, confirmed by optical coherence tomography.

Results The patient was offered the treatment alternative of vitrectomy, but she preferred to be reviewed conservatively. Three years after initial presentation, neither macular detachment nor subretinal fluid was evident in optical coherence tomography, while inner segment/outer segment (IS/OS) junction line was intact. Her visual acuity was improved from 6/24 to 6/12 in her left eye, remaining stable at the 6‐month follow‐up after resolution.

Conclusion This is a case of spontaneous resolution of longstanding optic disc pit associated macular detachment with significant visual improvement, postulating that the integrity of IS/OS junction line may be a prognostic factor for final visual acuity and suggesting optical coherence tomography as an indicator of visual prognosis and probable necessity of surgical management.
Vitreoretinal complications in hematology patients after hematopoietic stem cell transplantation
Authors: PARK YH , YOO YS , SHIN JA , LEE J
Published: August 2014

Purpose To identify vitreoretinal complications in patients after hematopoietic stem cell transplantation (HSCT).

Methods Patients with hematologic diagnosis after HSCT were enrolled this study at St. Mary’s Hospital, Korea from 2009 to 2012. Among them, we included the patients who have survived more than 2 years at least since they transplanted. The frequency and subgroup analysis of patients with vitreoretinal complications were done. From the medical records, we confirmed the prognosis of them. As a factor associated with vitreoretinal complications, the occurrence of ocular graft‐versus‐host disease (GVHD) was also analyzed.

Results Total 635 patients were included in this study. There were 207 patients with CMV viremia, 16 (2.52 %) patients was diagnosed as CMV retinitis among them. 24 (3.78 %) patients was diagnosed as retinal hemorrhage. In addition, there were 5 (0.79 %) patients with uveitis, 2 (0.31 %) patients with non‐proliferative diabetic retinopathy, 1 (0.16 %) patients with optic neuropathy, 1 (0.16 %) patients with retinal detachment, 1 (0.16 %) patient with central serous chorioretinopathy, 1 (0.16 %) patient with central retinal vein occlusion, 1 (0.16 %) patient with age‐related macular degeneration, and 1 (0.16 %) patient with endophthalmitis. Most of them had regular follow‐up without ocular treatments for retinal complications. In subgroup analysis, there was no significant difference in the incidence of ocular GVHD between groups which had vitreoretinal complications or not.

Conclusion The vitreoretinal complications is not usual event in patients who received HSCT. Most of them had good prognosis for retinal complications. The occurrence of vitreoretinal complications was not associated with ocular GVHD.
Mapping angiogenesis on choroidal membranes of a murine laser‐induced CNV model
Authors: TUNIK S , ARONSSON M , KVANTA A , ANDRE H
Published: August 2014

Purpose We investigated the expression and distribution of neoangiogenic molecules during the development of choroid neovascular (CNV) lesions in a laser‐induced mouse model of neovascular age‐related macular degeneration (AMD), with particular focus on the choroid of these lesions.

Methods Lesions were induced on C57BL/6 mice using laser photocoagulation. Animals were sacrificed and eye‐cups were dissected from enucleated eyes, and the choroids were shortly fixed. Choroids were immunostained for NG2 (pericytes), VEGFR2 (vascular endothelial growth factor receptor 2; sprouting endothelial cells(ECs)), or VEGF with co‐staining for CD31 (vascular ECs). lmages of the choroidal membranes were obtained by microscopy. Vascular permeability was also determined.

Results CNV lesions displayed positive staining for the four angiogenic markers studied. The distributions of the angiogenic markers were determined in comparison to the area of neovascularization, as observed by increased CD31 staining. Both NG2 and VEGFR2 displayed a radial progression, while VEGF displayed a uniform distribution across the choroidal membranes of the lesions in the studied times. Vascular permeability showed an increase concomitant with the increase in vascularization observed by immunostaining throughout the time‐course.

Conclusion Our data shows that the choroidal membranes of CNV lesions recover through a canonical sprouting angiogenesis pathway, in response to a VEGF‐mediated signal. ln addition, these membranes display an increasing radial endothelial sprouting with concomitant pericyte recruitment from the laser injury to the exterior of the lesions, in a time‐dependent. These results may have implications for the clinical understanding of CNV in patients with wet AMD.
Comparison of ocular tissue weights (volumes) and tissue collection techniques in commonly used preclinical animal species.
Authors: STRUBLE C , HOWARD S , RELPH J
Published: August 2014

Purpose Ocular pharmacokinetic and distribution studies are key elements for the development of ophthalmic drugs and are used to correlate drug levels in preclinical species with human dosages and exposures. The purpose of this study was to compare ocular tissue weights for five commonly used preclinical species using two collection techniques.

Methods Standard ocular tissues were collected from five males and five females of each species; New Zealand white (NZW) and Dutch Belted (DB) rabbits, beagle dogs, Gottingen minipigs, and Cynomolgus monkeys. Two collection techniques were used; a collection from fresh eyes (OS, immediately following enucleation) or a collection from frozen eyes (OD, following flash freezing). A specific procedure and collection sequence was followed for each technique.

Results Aqueous and vitreous humor, cornea, lens, iris‐ciliary body, retina, choroid, and sclera were collected from each species; these tissues represented mean values of 70.0‐82.0% and 84.3‐88.9% of the total eye weight, respectively, for fresh and frozen collection. Tissue recovery levels were consistently higher using the frozen collection technique. Mean combined male & female vitreous humor weights using the frozen collection were 1.41, 1.31, 2.22, 2.34, and 2.04 g for NZW & DB rabbits, dogs, minipigs, and monkeys, respectively. Other tissue weights will be compared.

Conclusion Comparative ocular tissue weights are presented for common preclinical species using fresh or frozen collection techniques. Vitreous humor and other tissue weights collected by the frozen technique accurately represent the weight (and volume assuming a VH density of 1) of the total tissue for comparative purposes to human vitreous volumes.
Temporal response of the phagocytic microglia in the axotomized rat retina: optic nerve crush vs. transection
Authors: NADAL‐NICOLAS FM , JIMENEZ‐LOPEZ M , SALINAS‐NAVARRO M , NIETO‐LOPEZ L , CANOVAS‐MARTINEZ I , SOBRADO‐CALVO P , VIDAL‐SANZ M , AGUDO‐BARRIUSO M
Published: August 2014

Purpose To analyze the appearance of phagocytic microglial cells (PMC) in rat retinas after optic nerve crush or transection.

Methods Retinal ganglion cells (RGCs) from adult Sprague Dawley rats were traced with fluorogold applied to both superior colliculi. One week later, the left optic nerve was either crushed (ONC, n=32) or transected (ONT, n=32). Rats were euthanized at 2, 5, 9 and 14 days after the axotomy (n=8/group). Retinas were dissected as flatmounts and Brn3a immunodetected to identify RGCs. Retinas were photographed for each signal. Brn3a+RGCs were automatically quantified and their distribution visualized by isodensity maps. The position of each PMC found in the ganglion cell layer (identified by their transcellularly labelling with fluorogold) was dotted on the retinal photomontages. These dots were counted and graphically represented with neighbour maps.

Results PMCs were observed at 2 days(43±8, ONT; 11±5, ONC). Their number increased quicker after ONT than after ONC in opposition with the loss of RGCs which was slower after ONC. The peak of PMCs was observed at 9 days after ONT and at 14 days after ONC (19,842±2534 and 19,757±1968, respectively). The appearance of PMCs and the loss of RGCs was highly correlated (r2=0.8 for both lesions). PMCs were observed across the retina and their distribution matched the retinal areas of RGC loss.

Conclusion ONC induces a slower loss of RGCs than ONT, and this is followed by a slower response of microglial cells.
Comparison of corneal power and astigmatism in normal eyes using 4 different devices
Authors: HAN KE , LEE HK , HWANG HS , SHIN MC
Published: August 2014

Purpose To compare corneal power and astigmatism in normal subjects obtained from dual Scheimpflug analyzer (Galilei), single Scheimpflug analyzer (Pentacam), optical low coherence reflectometer (Lenstar) and autokeratometer (AR)

Methods Forty‐eight eyes of 27 subjects were evaluated with 4 different devices. Steep, flat and mean keratometry (K) values and astigmatism magnitude were measured. Corneal power vectors, J0 and J45, were calculated using Jackson cross cylinder. Repeated‐measured ANOVA with Bonferroni post hoc analysis was performed to compare the measurements, and correlation was accessed by Pearson correlation test. Agreement was assessed by Bland‐Altman analysis and 95 % limit of agreement (LoA) was calculated.

Results Mean K values measured by Galilei, Pentacam, Lenstar, and AR were 44.34 ± 1.03 diopters (D), 44.52 ± 1.03 (D), 44.30 ± 0.98 (D), and 44.44 ± 0.92 (D), respectively. Steep K, J0, and J45 did not show significant differences (all p > 0.05), however, mean K, flat K, and astigmatism were significantly different (p= 0.002, 0.002, 0.005, respectively). All measured parameters were significantly correlated with each other (Pearson correlation test, all p < 0.05). For corneal power and astigmatism, 95% LoA varied from 1 to 2 (D).

Conclusion Even though the measurements of corneal power and astigmatism were correlated with each other, some values showed significant differences and the agreements were not good. Therefore, the measurements of each device couldn’t be used interchangeably in clinical practice.
Expression of HGF/c‐Met in control and keratoconus corneas
Authors: YOU J , ROUFAS A , WEN L , HODGE C , SUTTON G , MADIGAN M
Published: August 2014

Purpose Keratoconus (KC) is the most common primary degenerative corneal disease with a prevalence of around 1 in 2000 worldwide. A recent genome‐wide association study on potential genes associated with KC identified a significant association between KC and two single nucleotide polymorphisms in the promoter region of the HGF gene. The HGF/c‐Met pathway protects cells from apoptosis and is important to maintain epithelial homeostasis. In this study, we investigated if the HGF/c‐Met pathway is involved in KC by comparing HGF/c‐Met protein expression in control and KC samples.

Methods HGF and c‐Met immunoreactivities in control (n=5) and KC (n=10) corneas were imaged by confocal microscopy.Basal tears were collected by capillary micropipettes from control and KC patients (n=5 each), and HGF protein expression determined by Western blot. Intracellular c‐Met (the membrane bound receptor for HGF) expression was detected by extracting proteins from both control and KC corneal epithelium (n=5 each) followed by Western blot.

Results HGF and c‐Met were expressed in control and KC corneas. However,in KC obvious cytoplasmic staining of basal epithelium was noted compared to the more diffuse cytoplasmic epithelial immunostaining in control corneas. Western blot results showed that lower levels of HGF in KC tears compared to control tears, and the intracellular c‐Met expression was also weaker in KC cell lysates compared to controls.

Conclusion We find that HGF/c‐met expression patterns were altered between KC and control corneas, and their expression levels were reduced in KC tears and corneal epithelium cell lysates suggesting a role for this pathway in the pathogenesis of KC. Funding: Medical School of Sydney University, Sydney Eye Hospital Foundation, Lions NSW Eye Bank
Observational comparative study of different predictive scores of infraclinic keratoconus in refractive laser surgery in case of recused patients
Authors: CHENY T , ABRIEU M , RAMBAUD C , BERGUIGA M , SENDON D , THOUVENIN R , FROUSSART‐MAILLE F , RIGAL‐SASTOURNE JC
Published: August 2014

Purpose INTRODUCTION : The surgical laser treatment of refractive disorders is becoming more and more prevalent. Preoperative evaluation means are multiple and all seem promising in the detection of infraclinic keratoconus. Our purpose was to compare the different scores. SETTING : Review of cases, ophthalmology and refractive surgery unit, Percy Military Hospital, Clamart, France.

Methods MATHERIAL AND METHODS : Retrospective monocentric observational study, conducted between november 2013 and may 2014. Each patient benefited from an exhaustive corneal topography assessment : Pentacam® and a Belin/Ambrosio ehancement (P/B), Orbscan® and SCORE analyzer by Gatinel & Saad (O/S), and an Ocular Response Analyzer (ORA). A systematic analysis of the following was conducted : the thinnest point of pachymetry (TP), the value of maximum posterior elevation (MPE), the I‐S ratio (IS), the maximum keratometry (K max), the presence of SRAX, and the enantiomorphism.

Results RESULTS : 36 myopic patients, recused from laser refractive surgery, were included, or 72 eyes. Suspect cases added up to 31 patients for P/B, 32 for O/S, and 27 for ORA (or respectively 52, 55 and 40 eyes). There were 9 cases of discordance between the different scores. The averages were respectively : 502 +/‐ 47 µm for P, 26.81 +/‐ 7.46µm for MPE, 0.78 +/‐ 0.55 for IS, 44.6 +/‐ 1.8D for K‐max.

Conclusion CONCLUSION : Each of the exams and indices studied led us to detect infraclinic keratoconus, but in discordant cases, a more detailed analysis of the topographic map remains essential.
Translation of the therapeutic approach of scleral collagen crosslinking (SXL) from animal to human
Authors: RATTUNDE U , KORBER N , GOHLER C , KOCH C , KARL A , SCHULDT C , REICHENBACH A , FRANCKE M , WIEDEMANN P , ISELI HP
Published: August 2014

Purpose In our research project “collagen crosslinking of scleral tissue (SXL)”, the application of riboflavin and blue light has been proved as a possible therapeutic method to increase scleral stiffness. Nevertheless, it is necessary to develop a new application system applicable in human.

Methods Rheology was used to investigate changes of sclera stiffness after SXL treatment. An adapted and modified blue light irradiations system has been developed to apply various blue light intensities.

Results As a proof of principle, we demonstrate a dose dependent increase of scleral stiffness after application of various blue light energy dose rates. Increased biomechanical stiffness could be induced with light dose rates up to 200 mW/cm². However, the light application system used for animal surgery has serious limitations. The animal experiments revealed relevant technical parameters and helps to design a suitable substance and application system for usage in human.

Conclusion The results confirm the idea that SXL by riboflavin and blue light irradiation is an applicable method to increase biomechanical stiffness of scleral tissue and therefore, it might be a treatment for pathologic myopia. For the therapeutic application in patients a special substance application and irradiation system has to be refined and developed further.
Characterization of extracellular matrix remodelling enzymes in the sclera after collagen cross linking (SXL)
Authors: GOHLER C , KARL A , KORBER N , KOCH C , REICHENBACH A , WIEDEMANN P , FRANCKE M
Published: August 2014

Purpose High myopia is characterised by excessive eye growth and mechanically weakened, thinned and stretched scleral tissue. Enhanced chemical cross linking of collagen fibrils in the sclera (SXL) is a promising therapeutic approach to stiffen the sclera and to prevent eye globe elongation. Therefore, it is important to understand the role of collagen fibril producing fibroblasts and the extracellular matrix remodelling enzymes in normal and myopic eyes and after SXL treatment.

Methods We examined scleral tissue of normal rabbit eyes and after SXL treatment by means of histology and electron microscopy. We characterised expression profiles of cellular markers (e.g. Vimentin) and of relevant enzymes (e.g. MMPs) by means of RT‐PCR analysis and immunohistochemistry in cell cultures from human and rabbit scleral tissue.

Results We observed altered scleral collagen fibril profiles and activated scleral fibroblasts ‐ signs of remodelling processes after SXL treatment. Fibroblasts are capable to produce and secrete collagen and different matrix‐degrading and regulatory enzymes (e.g. MMP1‐3 and 9; TIMP1‐4; LOX).

Conclusion Significant remodelling processes were induced after SXL treatment and the role of each specific contributor/enzyme has to be determined for an efficient SXL treatment. increases scleral stiffness. We want to investigate the influence of relevant enzymes on remodelling processes after SXL to optimize the new and promising therapeutic approach.
Late diagnosis of donor‐to‐host herpes infection in a descemetic deep anterior lamellar keratoplasty (dDALK) procedure for keratoconus: case report.
Authors: MENICACCI F , SARNICOLA E , MENICACCI C , SARNICOLA V
Published: August 2014

Purpose To report a case of donor herpetic infection after descemetic deep anterior lamellar keratoplasty (dDALK) using the big‐bubble technique in a patient with no previous history of herpes simplex virus type 1 (HSV‐1) infection.

Methods A 39 year old man with a 15‐year history of keratoconus underwent an uncomplicated dDALK. Graft failure treated with excisional dDALK happened 3 times. Culture of failed donor corneas, bandage contact lens and stitches were tested for fungus and bacteria in all three explanted tissues. Polymerase chain reaction (PCR) for HSV‐1 DNA was performed only on the last failed corneal graft.

Results Four weeks after intervention patient developed a primary graft failure with corneal melting. Emergency DALK procedure was performed. Cultures were negative for fungus and bacteria. Graft failure occurred again during the early postoperative period. Another DALK procedure was performed. Cultures were again negative in removed tissues. In eight days the patient developed a third graft failure with corneal melting, so that a new DALK procedure had to be performed. PCR was positive for HSV‐1 DNA. Systemic acyclovir prevented a recurrence of infection and at the 6‐month and 1 year follow‐up, no signs of corneal graft failure were detected.

Conclusion HSV infection should be considered in the differential diagnosis with bacterial and fungal infection in early graft failure after DALK procedure. DALK allowed the repetition of corneal transplantation four times and provided enough endothelial cell density at 6‐month of follow‐up.
Adenovirus keratoconjunctivitis in relation with refractive surgery. Effects and treatment of sequelae
Authors: PEREZ NAVARRO I , DEL BUEY MA , HERERRA L , CARAMELLO C , ALMENARA C , IDOATE A , MARTINEZ M , ESTEBAN O , PEREZ GARCIA D , PINILLA I
Published: August 2014

Purpose Adenovirus keratoconjunctivitis (AK)can cause corneal opacities that sometimes remain in time, compromising the vision of the patient. The objetive is to show the different morphologic types of corneal affection as a consequence of AK in patients who have received refractive surgery,and to evaluate the application of refractive keratectomy with excimer laser as a possible treatment of the opacities and visual impairment caused.

Methods We analyze three examples of patients with visual impairment caused by corneal opacities secondary to adenovirus keratoconjunctivitis. The first case presents central nummular opacities without refractive history; opacities are treated,by photoablation myopic and associated hyperopic. The second case presents central corneal opacities after adenovirus keratoconjunctivitis, 10 years after PRK practice, causing myopic regression;the visual and refractive result emerges after a new laser photoablation. The third case shows the peculiar corneal fibrosis which appears after AK in a patient who received past LASIK treatment

Results In the cases of opacification due to superficial corneal fibrosis, good visual and refractive results are obtained through the use of superficial photoablation with excimer laser, with the associated application of mitomycin C

Conclusion The morphology of the lesions observed as a consequence of AK varies in patients with no history of refractive surgery, and in patients with a history of refractive surgery Lasik and surface techniques. Refractive PTK is an alternative to the treatment of opacities in case of suitable corneas
Laser in situ keratomileusis: epidemiology and risk factors of flap folds
Authors: SENDON D , RAMBAUD C , ABRIEU M , BERGUIGA M , FROUSSART‐MAILLE F , RIGAL‐SASTOURNE JC
Published: August 2014

Purpose Flap wrinkles can be seen in 0,2‐4% of LASIK cases. Our purpose is to evaluate flap folds through 7 femto‐second cases and make a review of the literature on the epidemiology.

Methods Retrospective monocentric review of 822 eyes who had flap created with the IntraLase FS60 femtosecond laser one month follow up were included between January 2012‐January 2014 in the Ophthalmology and Refractive Surgery Unit, Percy Military Hospital. Patients had an exhaustive examination with uncorrected (UDVA) and corrected distance visual acuities, spherical equivalent and mean keratometry (Km) were compared preoperatively and postoperatively. Flap thickness were measured with SD‐OCT and optical aberrations on Zyoptix Wavefront System.

Results 7 folds of 6 patients were observed (0.85% of LASIK procedures), 4 were horizontal, 1 vertical and 2 oblique. No trauma was found. All the folds involved the visual axis. Their UDVA was +0,2 logMAR (from +0,4 to 0). Mean spherical equivalent decreased from ‐4,9 D to ‐0,43 D, mean Km changed from 43 D to 39.75 D. Postoperative optical aberrations measured at 4.57 µm (+/‐ 2). Mean thickness measured to 120µm (+/‐ 8). The main causes are early trauma, flap desiccation and contraction, intraoperative misalignment, flap thinness, large photo‐ablation of myopia and cuts with microkeratome. The folds concern throughout its thickness and are the result of hyper‐hydration of proteoglycans, resulting in irregularity of Bowman's membrane and flap deformation.

Conclusion Flap folds are a potentially sight‐threatening complication. Rigorous surgical technique, education and post‐operative follow‐up would reduce their frequency, identify and treat them quickly to increase visual performance.
Treatment of corneal ulcers in ocular surface inflammation
Authors: LAZREG S
Published: August 2014

Purpose severe ocular surface inflammation can be lead to different diseases and can cause severe corneal involvement

Methods 5 cases of ocular surface inflammation with severe corneal ulcers resistant to conventional treatment , all treated with à new matrix therapy agent (cacicol 20%) 1 drop a day every other day for 4 weeks , with biomicroscopic records at D0 , D3, D7, D 15 and D30.

Results patients were aged between 18 to 66 years old, ocular surface inflammation was due to GVHD, severe Sjögren's Syndrome, Atopic keratoconjuctivitis, ocular pymphygoide and Stevens Johnson syndrome, all ulcers were chronic and rebels to different treatment ,at D7 we observed a decrease on VAs pain scale at D15 in all cases a total epitheliazitation of the ulcers ,

Conclusion CACICOL 20® is a new ophthalmic device, derived from RGTA based matrix therapy (large biopolymers engineered to replace heparan sulfates) , wich is a revolution in treatment of chronic ulcers, in our cases it has a double effect antalgic and regenerating;
Sclero‐corneal lenses’ supply for the treatment of keratoconjunctivitis sicca in patients with refractory ocular GvHD
Authors: RICHET M , MAGRO L , RANDON T , ERNOULD F , YAKOUB‐AGHA I , LABALETTE P
Published: August 2014

Purpose Keratoconjunctivitis sicca (KCS) due to chronic GvHD (cGvHD) is responsible for major alteration in quality of life of patients undergoing allogeneic stem cell transplantation . The conjunctival fibrosis induce impaired corneal and conjunctival epithelial surfaces. Treatment of KCS remains disappointing; variable success has been obtained with variety of topical treatments. Sclero‐corneal lenses bring a valid therapeutic option by creating a pre‐corneal reservoir of tears.

Methods We describe the safety and efficacy of Sclero‐corneal lenses in a retrospective analysis of 7 patients with KCS due to cGvHD. All patients had superficial punctate keratitis refractory to standard treatments. Evaluation of patients was carried out by the same ophthalmologist and hematologist. OSDI score was used to evaluate ocular symptoms and Oxford score to quantify corneal damage. Visual acuity "LOG MAR" was used for comparative purposes of the study.

Results All patients but one agreed to hold the lenses. The 12 eyes of the 6 remaining patients were equipped with lenses type ICD (LCS Company). All patients experienced an improvement in their quality of life with a clear improvement of dry‐eye symptoms. We observed 100% improvement in OSDI score with an average improvement of 67.08 points, 100% improvement or stability of visual acuity with an average gain of ‐0.23 LOG MAR acuity and 100% improvement or stability of the Oxford score with a mean gain of 1,917 points.

Conclusion Despite its limited size, this cohort of patients treated with sclero‐corneal lenses is promising. Whenever possible, this approach should be considered in patients experiencing KCS refractory to standard treatments in cGVHD.
Ocular protection index is related to ocular surface disease index in dry eye disease patients
Authors: BADIAN R , UTHEIM TP , RÆDER S , UTHEIM Ø , CHEN X , STOJANOVIC A , EIDET JR
Published: August 2014

Purpose To assess symptoms and signs in a Norwegian cohort of dry eye disease (DED) patients by investigating the relationship between Ocular Protection Index (OPI) and Ocular Surface Index (OSDI).

Methods DED patients of mixed etiologies were consecutively included in the study and defined as OPIhigh (OPI ≥ 1) or OPIlow (OPI < 1). All patients received an extensive ophthalmological work‐up. Groups were compared by using analysis of covariance (ANCOVA).

Results Three hundred and twenty nine (329) DED patients were included. Seventy‐four of the 329 patients (22%) were OPIlow, whereas 255 were OPIhigh (68%). The two groups did not differ from each other with respect to either age (P= 0.063), gender (P=0.099) or in the number of systemic prescription drugs used (P= 0.586). After controlling for the effects of gender, age and the number of systemic prescription drugs used OPIlow patients had significantly higher OSDI scores (16.9±2.0) than OPIhigh patients (13.5±1.1) (P= 0,002).

Conclusion A low OPI is related to a higher symptom load, as measured by the OSDI questionnaire.
The effects of lower lid laxity on the response to dry eye treatment
Authors: LEE N , YIM H
Published: August 2014

Purpose To compare the responses to dry eye treatment of patients sorted by the degree of lower lid laxity.

Methods Sixty patients were grouped into three groups according to the degree of lower lid laxity. Tear break‐up times (TBUT), Schirmer test (ST) scores, ocular surface disease index (OSDI) scores, and changes in OSDI score in each group were compared, before and at 3 months after treatment.

Results TBUT, ST, and OSDI scores were not different among the three groups at baseline. TBUT improved in each group at 3 months after treatment, and no differences between groups were found. ST scores were not increased after treatment, while OSDI were improved to 22.57±5.243, 31.16±11.353, and 37.85±13.342 in the no, moderate, and high laxity groups, respectively; these improvements were statistically significant (p=0.003, <0.001, <0.001, respectively). Patients with greater than moderate lower lid laxity saw the smallest improvement in response to dry eye treatment, as assessed by change in OSDI score (p=0.005 vs. moderate laxity group, p=0.005 vs. no laxity group).

Conclusion Lower lid laxity is one of the factors contributing to the manifestation of dry eye symptoms, independently of TBUT and ST scores.