bluuebunny/crossref_metadata_2025 huggingface dataset:
Mapping genomic loci related to variation in visual quantitative traits in an isolated island community of Croatia
Authors: VATAVUK Z , BENCIC G , PETRIC VICKOVIC I , LACMANOVIC LONCAR V , ANDRIJEVIC DERK B , SKUNCA J , ZRINSCAK O , BEDNAR I , KNEZEVIC T , POLASEK O , RUDAN I
Published: October 2007

Purpose: It has been hypothesized that isolated human communities are particularly favourable for identifying genetic variants underlying complex human traits and diseases because of their reduced genetic and environmental diversity. The aim of this study was to identify genomic loci that may control variation in visual quantitative traits in 1,057 examinees in isolated island of Vis, Croatia, by positional cloning.

Methods: Using refractometer, ultrasound and Canon CR‐DGI non‐mydriatic fundus retinal camera we obtained a number of visual quantitative and qualitative traits in our set of examinees. All measurements have been adjusted for potential confounders that were identifyied through an appropriate questionnaire. Both linkage analysis and and genome‐wide association approach were used (PLINK and GENABEL softwares) to identify genomic loci that may have significant contribution to the variation observed in those traits.

Results: A number of loci have been identified in the genome that approached formal significance levels after Bonaferroni correction of 10‐6. Those loci now require repeat in other populations to eliminate false positive findings, and further study in bioinformatics and functional genomics to understand their potential role in trait variation and possible development of pathological states.

Conclusions: This study showes that mapping genetic variants underlying complex human traits in isolated population is a feasible and powerful approach. We aim to expand our studies to other Croatian islands to further increase the power of the study.
Influence of platelets on the healing of dry eye of patients treated with topical eye drops of autologous Platelet‐Rich Plasma (PRP)
Authors: BATAILLE L , ALIO JL , PASTOR S , KLONOWSKY P
Published: October 2007

Purpose: To study the influence of high levels of platelets on patients suffering from dry eye and treated successfully with autologous PRP.

Methods: Platelet enrichment on autologous PRP of 16 patients (age 65±14) suffering from moderate to severe dry eye was evaluated and different dry eye parameters (symptoms, BCVA, fluorescein staining, impression cytology) were correlated with this value. 7 patients had lower that 1.3 fold platelet enrichment on their autologous PRP (low platelets (PLTs) group) and 9 had more that 1.75 fold platelet enrichment (high PLTs group).

Results: On the low PLTs group (7 patients), 50% of them showed a significant improvement of symptoms, 45% showed more than 1 line of BCVA improvement and 35% showed full disappearance of fluorescein staining. On the high PLTs group (9 patients), 78% of patient showed a significant improvement of symptoms, out of 10 patients evaluated for BCVA, 50% of them gained more that 2 lines of vision and 71% experienced a full disappearance of fluorescein staining.

Conclusions: Autologous PRP has been shown to be very effective on dry eye treatment. On this study we show that high levels of platelets present on this biological product play an important role for the healing of dry eye. Other components of autologous PRP such as growth factors and vitamins should also help for improving these patients symptoms and main clinical signs.
Strategies for improving intraindividual reproducibility in laser Doppler flowmetry measurements
Authors: PEMP B , MAAR N , WEIGERT G , LUKSCH A , RESCH H , GARHOFER G , ORGUL S , SCHMETTERER L
Published: October 2007

Purpose: Scattering of blood flow data as assessed with laser Doppler flowmetry (LDF) in humans is a problem in many studies using this technique. We set out to reduce variability in LDF data by partializing out the effect of the total returning light level (DC) on LDF parameters in the choroid.

Methods: In 20 healthy subjects choroidal blood flow was measured at different DC values using a portable confocal LDF device. To reduce scattering of data partializing out the effect of yield, defined as DC/gain, firstly a previously described method based on a third order polynomia fit using all obtained data was applied. Secondly a new method based on a linear fit obtained for each subject individually was used.

In addition, these correction procedures were applied retrospectively to the data of a recent study investigating the effect of a nitric oxide (NO) synthase inhibitor on choroidal and optic nerve head blood flow parameters.

Results: Both methods were successful in reducing scattering of LDF parameters in the choroid with varying baseline DC values. In addition, both methods minimized scattering of the effect of the NO synthase inhibitor on ocular blood flow parameters as analyzed retrospectively. Whereas, however, the previous approach altered the magnitude of the mean change induced by the NO synthase inhibitor to higher values, the new method preserved the originally reported effect.

Conclusions: When systematic changes in DC occur after an intervention one needs to be careful in interpreting the obtained data. The approach presented here may represent an effective, easily applicable and valid way to reduce scattering of data from using LDF to assess blood flow in the posterior pole of the human eye.
Variability of ocular perfusion measurements in glaucoma and healthy subjects
Authors: SCHMETTERER L , FUCHSJAEGER‐MAYRL G
Published: October 2007

Purpose: Variability is a major problem in ocular blood flow measurements. It is an important determinant of sample size in clinical trials and may limit clinical usefulness if it is too high. We set out to compare the short‐term reproducibility of blood flow parameters assessed with scanning laser Doppler flowmetry and laser interferometric measurement of fundus pulsation between healthy young subjects and glaucoma patients.

Methods: Measurements in 140 healthy male non‐smoking subjects and 140 patients with primary open angle glaucoma were included in this analysis. From two consecutive measurements performed within 5 minutes the coefficient of variation in an individual was calculated for each outcome parameter. These included the fundus pulsation amplitude (FPA), the flow, volume and velocity in the rim and the cup.

Results: Mean coefficients of variation were between 3.2% and 23.8 % for all outcome parameters in healthy subjects and between 4.9% and 34.3% in the patients. FPA showed the highest reproducibility although individual coefficients of up to 22.5% and 34.7% were observed in healthy subjects and glaucoma patients, respectively. With scanning laser Doppler flowmetry velocity was better reproducible than volume or flow. Individual coefficients of variation for flow values were as high as 87.5% in healthy subjects and 132.2% in glaucoma/ocular hypertension patients.

Conclusions: Our data indicate that in healthy subjects the selected techniques provide better reproducibility than in patients with ocular disease. This needs to be considered in sample size calculation for clinical trials. In addition, the high individual differences in flow parameter readings observed in some subjects limit the use of the techniques in clinical practice.
Lacrimal gland adenocarcinoma
Authors: GARCIA‐ALVAREZ C , SANCHEZ‐MANNARELLI F , BLANCO‐MATEOS G , BORREGO H , ESTEBAN R
Published: October 2007

Purpose: To expose a clinical case. Lacrimal gland adenocarcinomas are tumors with epithelial origin end aggressive behavior and poor prognosis. Perineural invasion lead to diffuse infiltration of the orbit worsening the patient prognosis and used produce pain as main symptom.

Methods: Clinical case

Results: A patient of 75 years was referred by an orbital inflammation resistant to three months of systemic steroids treatment. The orbital CT demonstrate a mass in the lagrimal gland with signs of periglandular bone infiltration. A lateral orbitotomy show a mass of 15 x 12 mm, classified as adenocarcinoma of lagrimal gland with affected surgical borders in the pathologic study. Complementary external radiotherapy was done. In three months the patient developed palpebral edema and pain at the orbital region. The new CT demonstrated local recurrency and the systemic extension study was negative. However seven months later the patient died due to lung metastasis.

Conclusions: Lacrimal gland adenocarcinomas are tumors with aggressive clinical behaviour. When they develop perineural invasion, local control of the disease is difficult. In spite of the surgery and the complementary radiotherapy these tumors have a great tendency to local recurrency and systemic extension.
LASIK‐dry eye: fact or fancy
Authors: REGINALD AY , TIFFANY JM , ROSEN PH , BRON AJ
Published: October 2007

Purpose: To review the evidence for dry eye after refractive surgery.

Methods: A review of the literature.

Results: Irritation and ocular surface staining after LASIK is termed LASIK‐dry eye, treated with artificial tears and/or punctal plugs. Symptomatic recovery takes about 6 months. It has been attributed to a loss of afferent drive to the lacrimal gland and blink mechanism. Waking lacrimal secretion is stimulated by reflex sensory inputs from the ocular surface and nose. The rich innervation of the cornea, compared to the conjunctiva, determines that corneal incision causes significant loss of drive from the ocular surface, gradually restored by corneal re‐innervation.

While LASIK‐dry eye is a true entity, LASIK patients also suffer from LASIK‐induced neuroepitheliopathy or LINE, a neurotrophic state due to interruption of trophic, sensory nerves. The conditions are not mutually exclusive. The hallmark of LINE is the presence corneal staining confined to the flap and sparing the hinge region. Tear Break Up Time (TBUT) is normal or reduced and the Schirmer test is normal. The hallmark of LASIK‐ dry eye is staining of the interpalpebral conjunctiva, with or without interpalpebral corneal staining, accompanied by a reduced TBUT and Schirmer test and increased tear osmolarity. Pre‐existing tear film instability is a predictor of post‐LASIK dry eye and pre‐existing dry eye is a predictor of a chronic, post‐LASIK dry eye state, associated with a greater risk of refractive regression.

Conclusions: Post‐operative dry eye following LASIK or other refractive procedures is predictable and demands that all patients are assessed preoperatively for the signs of tear instability and dry eye. Preoperative detection permits a more accurate prognosis and the initiation of prophylactic measures.
Bilateral retinoblastoma: successful conservative treatment of both eyes
Authors: DEFRANCESCO S , HADJISTILIANOU T
Published: October 2007

Purpose: Conservative treatment (focal therapy, local and systemic chemotherapy, radiotherapy) is today the standard in Retinoblastoma treatment. Preservation of both eyes is unfortunately, not always , possible.

Methods: .

From 1959 to 2007, 442 cases of retinoblastoma have been diagnosed and treated at the Retinoblastoma Referral Center of the University of Siena. 175 cases were bilateral.

Results: 25 out of 175 bilateral cases have been conservatively treated. Age at diagnosis, sex, hereditary, stage at diagnosis (Reese Classification and ABC Classification), remission patterns and therapeutic protocol are reported. The age at diagnosis ranged from 4 days to 15 months (mean age: 5.4 months).

8 out of 25 were females, 17 out 25 were males. 13 out of 25 were familial cases. Stage at diagnosis (50 eyes) was I in 16 eyes, II in 12 eyes, III in 8 eyes, IV in 11 eyes, V in 3 eyes. 25 out of 25 received chemotherapy and focal therapy according to the Italian protocol. 12 out of 25 relapsed. 9 out of 12 received new cycles of focal and chemotherapy. 2 out of 12 received also brachytherapy. In 2 out of 12 subconjuctival carboplatin has been used. In only 1 case (familial case)external radiotherapy was requested and the child died for a second tumor one year later. 5 out of 25 developed new foci, immediately treated only with focal therapy.

Conclusions: The prognostic factors for successful conservative treatment are evaluated.
Ocular hemodynamic effects of nitrovasodilators in healthy subjects
Authors: POLSKA E , KISS B , KOCH B , SCHMETTERER L
Published: October 2007

Purpose: Previous studies on the ocular hemodynamic effects of nitrates showed partially contradicting results. The aim of the present study was to investigate the effect of nitrovasodilators on choroidal and optic nerve head (ONH) blood flow.

Methods: The study was performed in a randomized, placebo‐controlled, double masked, 4‐way crossover design in 12 healthy male subjects. Nitroglycerine, isosorbide dinitrate or sodium nitroprusside were administered intravenously in stepwise increasing doses on different study days. Physiologic saline solution was used as placebo control. To assess choroidal and ONH microcirculation, laser Doppler flowmetry measurements were performed. Laser interferometric measurements of fundus pulsation were used to assess pulsatile choroidal and ONH blood flow. Ocular perfusion pressure (OPP) was calculated as OPP=2/3MAP‐IOP. Thereafter a parameter of vascular resistance (R) for each measured blood flow parameter (BF) was calculated as R~OPP/BF.

Results: Placebo administration did not change any of the measured parameters. We observed small but significant reduction of IOP during the infusion of sodium nitroprusside. The pulsatile choroidal blood flow decreased significantly during the infusion of isosorbide dinitrate (–8.1%) and sodium nitroprusside (–4.3%). The pulsatile ONH blood flow decreased significantly only during the infusion of sodium nitroprusside (–5.7%). In addition, we observed a significant reduction of all calculated parameters of vascular resistance during the infusion of each nitrovasodilator (maximal decrease: –16% to –29%).

Conclusions: An intravenous infusion of nitroglycerine, isosorbide dinitrate or sodium nitroprusside caused a significant reduction of vascular resistance in the ONH and the choroid.
Optic nerve reflectivity variations during diffuse luminance flicker stimulation
Authors: BONAIUTI M , ROVATI L , RIVA CE
Published: October 2007

Purpose: Neurovascular coupling at the optic nerve is the mechanism that adjusts blood flow in the microcirculation of the optic nerve to support the neural activity induced by vision.

Our aim is to assess the variations of the optic nerve reflectivity in the near‐infrared during diffuse luminance flicker stimulation.

Methods: One informed and consenting male subject aged 29 was involved in the study so far. A commercial fundus camera (Topcon, Japan), modified for the purpose of the study, was used to carry out 770‐nm reflectivity measurements from the subject’s optic disk and peripapillary region. Neural activity was evoked by diffuse flicker stimulation (2Hz and 12Hz) in the green spectral region (535nm). The measurement protocol consisted of three periods: 20s baseline followed by 60s diffuse flicker stimulation and 20s recovery.

Results: During flicker stimulation we observed a decrease in optic nerve reflectance of about 8% at 2Hz and about 6% at 12Hz with respect to the measured baseline.

Conclusions: We report a significant decrease in the optic disc and peripapillary reflectance during diffuse visual stimulation at diverse frequencies. These variations could be induced by an increase in blood flow in the microcirculation of the optic nerve.

The authors gratefully acknowledge the support of the Fondazione Cassa di Risparmio in Bologna, Italy.
Impaired cytokine production of tumor infiltrating lymphocytes in a model of primary intraocular B‐cell lymphoma
Authors: TOUITOU V , BODAGHI B , DE KOZAK Y , CAMELO S , LEHOANG P , FRIDMAN C , FISSON S
Published: October 2007

Purpose: The immune microenvironment is thought to play a major role in promoting tumor growth. To evauate the role of this microenvironment in Primary intraocular lymphoma (PIOL) condition and characterize the cytokine polarization of infiltrating T‐lymphocytes (TIL), a murine model of intraocular B‐cell lymphoma was developed in immunocompetent hosts.

Methods: Intravitreal injection of a syngeneic lymphomatous B‐cell line in immunocompetent mice was performed. Clinical, histological and flow cytometric analysis were performed in order to characterize the tumoral invasion and the immune infiltration. Cytokine production of ocular cells was investigated by RT‐PCR and fluorescent immunoassay with or without stimulation by anti‐CD3 plus anti‐CD28 antibodies.

Results: Intraocular lymphoma developed in all eyes injected by lymphomatous B‐cells. Up to 15% of living cells were T‐lymphocytes. Cytokine profile analysis of the supernatant of ocular cells cultured ex vivo demonstrated the presence of IL10, IL6, IFNγ, and TNFα. Stimulation with anti‐CD3/anti‐CD28 antibodies increased the IFNγ level, and led to the induction of IL2 production, completing the type 1 (Th1/Tc1‐like) pattern of cytokine expression observed. IL6 and IL10 levels were not modified. IL12p70 and IL4, potent Th1 or Th2 differenciating factors, were undetectable even after stimulation.

Conclusions: Our results suggest that TIL from intraocular B‐lymphomas are characterized by a Th1/Tc1 like profile that could be partially inhibited in vivo. These data raise the possibility of an in situ T‐cell immunostimulation in order to reactivate the Th1/Tc1 lymphocytes and improve the intraocular anti‐tumoral immunity
Overview of therapeutics for improving the orbital volume in the socket syndrom
Authors: MOURIAUX F
Published: October 2007

Purpose: After the disfiguring orbital procedures of enucleation or evisceration, the cosmetic results of reconstructive surgery are often unsatisfactory because of a discrepancy between the volume of the orbital cavity and that of the orbital implant used to replace the eyeball. This result in typical findings of the postenucleation socket syndrome (PESS) : enophthalmos, backward tilting of the prosthesis, unsightly depression on the superior sulcus, malposition of the upper eyelid with retraction or ptosis, and stretching of the lower eyelid causes by the gravitational pull of the prosthesis.

Methods: Several pathophysiologic mechanisms have been proposed to account for these findings including volume deficit related to the eye loss, orbital fat atrophy and rotary displacement of the orbital contents, contraction of orbital structures.

Results: We will describe the many procedures proposed to restore the orbital volume : placement of a secondary larger implant, injection of fat, injection of hyaluronic acid, , subperiostal or intra orbital implants. We will describe the advantages and disadvantages of each one.

Conclusions: PESS is not a fatality. It can be restore by surgery.
Predicting the prognosis of ciliochoroidal uveal melanoma by its clinical characteristics: a European ophthalmic oncology group collaborative study
Authors: KIVELÄ T , KUJALA E , DESJARDINS L , DAMATO B , BECHRAKIS N , GRANGE JD
Published: October 2007

Purpose: To assess clinical characteristics independently associated with mortality from uveal melanoma using a large contemporary European dataset in order to improve future classifications.

Methods: Data of 8340 patients who had a choroidal and ciliary body melanoma managed by one of five participating ocular oncology centers directed by members of the European Ophthalmic Oncology Group (OOG) were collated. Variables requested included date of treatment and last follow‐up, survival status, largest basal tumour diameter (LBD), tumour thickness, ciliary body involvement and extraocular extension. Data were analysed with the product‐limit method and Cox regression.

Results: Valid LBD and thickness was available for for 7922 and 8111 melanomas, and ciliary and extraocular extension for 7418 and 6087 tumours, respectively. Complete data for all 4 variables were available for 5469 tumours (66%). Mean follow‐up time was 4.0 years (interquartile range, 1.5‐7.3). In Cox regression, all variables were significantly (P<0.0001) and independently associated with melanoma‐related mortality. Covariate‐adjusted hazard ratio (HR) was 1.15 for LBD and 1.06 for thickness (each 1 mm increase), and 1.72 for ciliary body involvement and 2.29 for presence of extraocular extension (yes or no).

Conclusions: Choroidal and ciliary body melanomas may effectively be categorised by LBD and thickness, and subcategorized by presence of ciliary body and extraocular extension. All four variables are recommended to be included in future clinical classifications of uveal melanoma. How ciliary body and extraocular extension could be collaboratively coded in more detail remains to be discussed.
A case of 2 brothers with congenital horners syndrome
Authors: PIERCE CO , SINCLAIR N , EVANS A
Published: October 2007

Purpose: To present a case of two siblings diagnosed with Congenital Horner's Syndrome. The condition developing in related patients has only been previously described once in the literature.

Methods: The older brother presented at 9 months to his GP with anisocoria. The left pupil appearing smaller than the right. There was no history of birth trauma or any neonatal concerns. The younger sibling was later referred after he was observed to have anisocoria, again the left being the smaller pupil. Both patients were term deliveries with normal labour and no postpartum problems.

Results: Pharmocological testing with cocaine 10% confirmed the diagnosis of Horner's syndrome.

Laboratory and radiological examinations performed by the paediatrician did not reveal any abnormality.

Conclusions: This case proposes a familial predisposition to the development of Horner's Syndrome and warrants future investigation into the cause.
Anti‐TNF‐alpha therapy for exudative ARMD
Authors: MISSOTTEN T , BAARSMA GS , VINGERLING JR , MARTINEZ‐CIRIANO JP , VAN HAGEN PM
Published: October 2007

Purpose: Angiogenesis is a major pathway in the pathogenesis of exudative age related macular degeneration (ARMD). There is evidence of an important inflammatory component as well. In ARMD patients with co‐existing inflammatory diseases treated with anti‐TNFa, a positive effect of these drugs on exudative ARMD was reported. As theoretical and clinical elements provided a rationale for the use of anti‐TNFa medication in ARMD, a prospective non‐randomised study was started.

Methods: A non‐randomised pilot study (calculated n=40) included patients with active CNV in ARMD. Treatment consisted of Infliximab IV, standard dose/scheme, for 1 year. ETDRS VA, contrast sensitivity, OCT, Fluorescein/ICG angiography, QOL and serological examinations were performed at set time points according to an IRB‐Ethical committee approved protocol. All patients were aware of the standard of care (intravitreal anti‐VEGF injections/risk endophthalmitis 1/1000) and the experimental nature of this study. All participants could switch to anti‐VEGF therapy at any time.

Results: Compared to baseline, change in visual acuity (ETDRS lines) was 0.04±0.5 ; 0.04±1.0 ; ‐0.33±1.0 ETDRS lines at 2 (n=20),4 (n=12) and 6 (n=6) months after start of Infliximab.

1 patient switched to anti‐VEGF therapy when disease remained active. 2 patients left the study for unrelated causes.

Conclusions: Preliminary results of this non‐randomised prospective study using IV anti‐TNFa therapy for exudative ARMD are promising. So far, in all but one patient, stabilisation of disease and VA could be found. Final study results are necessary to confirm these preliminary results. If confirmed, a combination of anti‐VEGF and anti‐TNFa therapy could be an attractive treatment modality for ARMD.
Profile of the Spanish ophthalmologist dedicated to retinal pathology. Preliminary results
Authors: SANCHEZ CHICHARRO DI , PASTOR JIMENO JC , FERNANDEZ I , ROJAS J
Published: October 2007

Purpose: Define the profile of ophthalmologists dedicated to retinal pathologies

Methods: After approval of the Spanish Society of Retina and Vitreous(SERV) a data base of professionals dedicated to treat retinal diseases was created from three sources: members of SERV, V‐R specialist according to pharmaceutics companies and suggested by well known V‐R specialists. A confidential questionnaire was sent. We used Chi‐squared and Fisher’s Exact test for qualitative variables and non‐parametric Kruskall Wallis test for quantitative variables

Results: 490 possible V‐R specialist were identified, obtaining 248 answers. The answers belonged to teaching hospitals 61%, non‐teaching hospitals 22%, teaching private institute 5.4%, non‐teaching private institute 11%. The mean population covered by public centres was 230.000 habitants, with a mean of 14.5 ophthalmologists and a median of 4 V‐R specialists per centre. 82% of V‐R specialist finished their training after 1980. 93.5% received V‐R training: residency (81%), medical retina master(13.8%), surgical retina master(11.6%) and from expert colleagues(63.3%). The preferential clinical practise was: medical retina 23%, surgical retina 12%, both 65%. 93% attend V‐R special consultation every week. 22% practice retinal surgeries, 14% cataract surgeries and 62% both. 79% practice vitrectomies(80/year), 84% intravitreal injections(2/week), 45% photodynamic therapy PTD(2.5/week) and 88% prescribe PDT(1/week). 90% is member of the Spanish Society of Ophthalmology

Conclusions: We approximately know the number of ophthalmologists dedicated to retinal pathologies, their specialist training and their clinical activity
Effects of primary open‐angle glaucoma on the globe, cross sectional area and morphology of the optic nerve and volume of the lateral geniculate body: a longitudinal study
Authors: CEZAYIRLI E , TUGLU I , GUNGOR K , VAROL T , BEKIR N
Published: October 2007

Glaucoma is a group of disorders that lead to damage to the optic nerve, which, in turn, causes vision loss that may progress to blindness. Glaucoma is characterized by increased pressure within the globe.

Open‐angle glaucoma is by far the most common type of glaucoma. In open angle glaucoma, Schlemm channels in the irido‐corneal angle gradually narrow with time, impairing the drainage of the aqueous humor. The

buildup of aqueous humor causes an increase in the intra‐ocular pressure. This increased pressure pushes on the junction of the optic nerve and the retina, reducing the blood supply to the optic nerve.

Twelve patients with primary open‐angle glaucoma and twelve age‐, sex‐ and stature‐matched healthy controls had high resolution MRI of the eye. T1 and T2 weighted MR images were acquired with a 1.5 Tesla imager (GE Medical Systems, Milwaukee, USA) using inversion recovery and fast spin echo sequences. Linear measurements of the distance between the angles formed

by iris and ciliary muscle, depth of the anterior chamber, thickness and diameter of the lens, distance between the anterior and posterior poles of the globe were performed. Cross‐sectional area of the optic nerve was calculated at 5 mm anterior to the optic chiasm using planimetric methods. The boundaries of the lateral geniculate body were delineated on orthogonal images and its volume was measured by multiplying the slice thickness with the area of each section. MR imaging and measurement protocol was repeated a year later to examine the changes.

No significant changes were found in distance between the irido‐corneal angles, anterior chamber depth, lens thickness and diameter, and the distance between the anterior and posterior poles of the globe between the

first and second scans among the patients or controls. We found a significant difference between patients and controls in the cross sectional area of the optic nerve in both scans. There was a decrease in the cross‐sectional area of the optic nerve in the patients but not controls. No significant changes could be demonstrated in the volume of the lateral

geniculate body.
Genetic markers for proliferative diabetic retinopathy in type 2 diabetes
Authors: GLOBOCNIK PETROVIC M , HAWLINA M , PETERLIN BORUT , PETROVIC D
Published: October 2007

Purpose: The purpose of this cross–sectional study was to define genetic markers of advanced proliferative diabetic retinopathy in patients with type 2 diabetes.

Methods: In retrospective study 186‐386 unrelated Caucasians with type 2 diabetes were enrolled and divided into 2 groups: advanced PDR (diabetics with PDR in wich vitrectomy was performed) and control group (diabetics with duration of diabetes of more than 15 years, without retinopathy).

The PCR was used to analyse candidate genes: gene polymorphism G‐174C of the interleukin –6 (IL‐ 6), ‐553 T/A, –834 T/A and ‐921 C/G of the beta fibroblast growth factor (BFGF), 634 C/G and –2549 insertion/deletion of the vascular endothelial growth factor (VEGF), (AC)n of the aldose reductase, K469E of the intercellular adhesion molecule (ICAM), Bgl II of the α2β1 integrin, –429 T/C and –374T/A of the receptor of advanced glycation end products (RAGE) and mutations C282Y and H63D of the hemochromatosis.

Results: Genetic risk factors for PDR in Caucasians with type 2 diabetes were the alele Z‐2 of the aldose reductase (AC)n gene polymorphism (OR 2.0, 95% confidence interval 1.4‐3.8; p = 0.03), the C282Y mutation of the hemochromatosis gene (OR = 3.0, 95 % confidence interval = 1.2‐8.0; p = 0.02) and the genotype EE of the E/K ICAM polymorphism (OR 2.3, 95% confidence interval 1.1‐4.7; p = 0.025). We failed to demonstrate other tested gene polymorphisms as genetic risk factors for PDR in Caucasians with type 2 diabetes.

Conclusions: Gene polymorphisms of the aldose reductase, the ICAM, and the hemochromatosis mutations could be used as genetic markers for PDR.
Corneal molding and crosslinking
Authors: BARRAQUER RI , LAMARCA J , SALVADOR B , ALVAREZ DE TOLEDO JP
Published: October 2007

Purpose: To develop an experimental setup in human donor eyes to study the feasibility of combining corneal crosslinking (CCL) with molding techniques such as orthokeratology and intracorneal arcuate implants.

Methods: 6 pairs of fresh human donor eyes with corneas unsuitable for transplantation but otherwise normal were maintained at constant 20 mm Hg intraocular pressure (IOP). The epithelium was removed and an orthokeratologic PMMA contact lens of 11.8 mm diameter and 10 mm main curvature radius was fixed to one cornea of each pair with 6 sutures of 9‐0 vicyl. A standard CCL protocol (0.1 riboflavin phosphate, 370 nm UVA at 3 mW/cm2 for 30 minutes) was applied simultaneously to both corneas. We measured pre‐ and postoperative IOP, central pachymetry, corneal topography (EyeSys), corneal hysteresis (CH) and resistance factor (CRF) (ORA).

Results: Average topographic cylinder (SimK) went from 1.66 diopters (D) to 2.01 D and from 1.55 to 1.06 D pre‐ to postoperatively, respectively in the orthoK‐CCL and CCL‐only corneas. Average maximal K value changed from 44.8 to 43.7 D in the orthoK‐CCL and from 43.8 to 43.4 in the CCL‐only group. None of these differences was statistically significant. Average CH went from 11.0 to 13.4 and from 9.0 to 13.7, respectively in the orthoK‐CCL and CCL‐only groups, while CRF went from 11.9 to 14.9 and from 10.7 to 14.6 respectively. Both groups showed a significant increase in pre‐ to postoperative CH and CRF, without significant differences between them.

Conclusions: An experimental setup has been devised, able for testing combined CCL and corneal molding techniques in donor human eyes. Corneal molding by a sutured standard orthokeratology contact lens combined with CCL does not appear to induce a permanent change in corneal curvature parameters.
Vitreoretinal management in osteo‐odonto‐keratoprosthesis surgery
Authors: WONG D
Published: October 2007

Purpose: To review the strategies, problems and technical issues in dealing with vitreo‐retinal pathology in eyes before, during and after osteo‐odonto keratoprosthesis (OOKP) surgery.

Methods: A retrospective review of eight consecutive cases in which vitreo‐retinal intervention was required in the OOKP programme in the Singapore National Eye Centre.

Results: Six eyes had retinal detachments. Three of these had limited previously untreated retinal detachments with traction, detected on b‐scan ultrasonography. Repair of the retinal detachments preceded completion of the OOKP procedures although one eye required a repeat vitrectomy for a recurrent detachment with the prosthesis in place. One eye had a massive choroidal haemorrhage resulting in abortion of OOKP stage two surgery. The choroidal haemorrhage resolved, leaving a localized traction‐associated retinal detachment that was repaired during repeat stage two surgery. Two eyes had prior retinal surgery for presumed detachments with silicone oil in place prior to OOKP surgery. Stage two surgery was completed with assessment and confirmation of stability of retinal pathology.

Two eyes required vitreo‐retinal intervention for endophthalmitis. One developed infection after stage two surgery and was successfully salvaged. The other developed endophthalmitis after endoscopic cyclophotocoagulation for glaucoma 18 months after stage two surgery. This eye was lost in spite of aggressive intervention.

The use of temporary keratoprostheses and vitrectomy endoscopes during surgery was necessary in most of these eyes.

Conclusions: OOKP surgery presents challenges for the vitreo‐retinal colleague. Assessment of the anatomical and functional integrity of the retina prior to and often after OOKP surgery is hampered. An accurately interpreted b‐scan ultrasound examination provides the most useful information. Vitreo‐retinal surgical intervention is technically demanding and requires the use of temporary keratoprostheses and endoscopes. An individualized and realistic management strategy has to be derived for patients with vitreo‐retinal pathology when OOKP surgery is embarked upon.
Genes and gene‐environmental interactions for retinal diseases
Authors: LIEW G
Published: October 2007

Purpose: To review the latest developments in identifying genes and gene environment interactions on risk of Age

related macular degeneration (AMD).

Methods: Review of the literature and some original data from the Blue Mountains Eye Study.

Results: One of the major successes of the Human Genome Project is the identification of novel genes related to risk

of AMD. At least two genes have been consistently identified in most studies to date, and a number of other candidate

genes are being investigated. CFHY402H on chromosome 1 is the most consistently identified gene, and many studies

have found a single copy of the at risk allele confers 2‐3 fold higher risk of AMD, particularly drusen development.

A DNA variant on chromosome 10 at the LOC387715 locus also appears to confer similar risk of AMD, with a stronger effect on progression to neovascular AMD than geographic atrophy. A number of other genes may also be related to AMD risk (e.g. APOE). CFHY402H codes for a variant of complement factor H, a key molecule in the alternative complement pathway. Certain CFH haplotypes may be protective against AMD. The gene product of LOC387715 is unknown, but evidence suggests it may be HTRA1, a serine protease. Finally, the currently available evidence suggests that CFHy402H does not interact with smoking to increase risk of AMD, whereas a few studies have indicated a LOC387715 interaction with smoking. CFHY402H may interact with obesity, with increased risk in persons with body mass index >=25, and potentially with higher fish intake.

Conclusions: CFHY402H and LOC387715 may explain the majority of cases of AMD progression. There is some evidence that CFHY402H may interact with obesity, whereas LOC387715 may interact with smoking, to increase AMD risk.
Retinal oximetry in humans: effect of laser
Authors: HARDARSON SH
Published: October 2007

Purpose: According to theory, laser treatment of the retina decreases the demand for oxygen and increases available oxygen for the remaining retinal tissue. Animal studies have shown that preretinal or intraretinal partial pressure of oxygen (PO2) decreases following experimental branch retinal vein occlusion (BRVO) and the PO2 rises again following laser treatment. Confirming the beneficial effect of laser on retinal oxygenation in humans has been difficult because practical non‐invasive technology for oxygen measurements has been lacking. Our research group has studied retinal oxygenation in humans with retinal vein occlusion.

Methods: The retinal oximeter is composed of a fundus camera, beam splitter and a digital camera. It yields fundus images with isosbestic and non‐isosbestic wavelengths of light simultaneously. Custom‐designed software analyses the images and estimates haemoglobin oxygen saturation in retinal vessels. Measurements have been made on 25 patients with retinal vein occlusion, in some cases before and after laser treatment.

Results: In the 5 patients with BRVO, who were measured both before and after laser, the oxygen saturation in affected venules rose from 45±10% (mean±SD) before laser treatment to 53±6% after treatment (p= 0.041). Cases of hemivein and central vein occlusion have shown low oxygen saturation before laser and increased oxygen saturation after laser.

Conclusions: The preliminary data indicates that, in some cases, low oxygen saturation is measureable in venules affected by retinal vein occlusion and that the saturation increases after laser. In some cases, notably where clinical signs are mild, the saturation appears to be normal even if no treatment has been applied but further studies are needed to establish the variability.
Endoscopic dacryocystorhinostomy and balloon‐dacryocystorhinostomy and transcanalicular DCR
Authors: UNGERECHTS R
Published: October 2007

With the development of miniaturisation of instruments endoscopic techniques got more and more important in ophthalmology. In this abstract endocanalicular endoscopic techniques will be presented. The significance of an endoscopic diagnostics will be shown.

Developments in the ongoing development in endonasal surgery made it possible that the success rate in internal endonasal Dacryocystorhinostomy is similar to those of an external DCR.

With the possibilities of endocanalicular endoscopy of the lacrimal duct and the options in surgery which result from that even more options opened up. These minimised the surgical effort and the postoperative rehabilitation. Judging the actual situation of the mucosa endoscopically regarding the position and degree of the stenoses there are different possibilities in rechanneling. With stenoses of the canaliculus or the lacrimal sac there’s the possibility of using the Erbium‐YAG‐Lasercaryoplasty. With subtotal stenoses which show clinically as total stenoses the rechanneling with a miniaturised drill is indicated, a Microdrilldacryoplasty. Both methods have a success rate of 78‐80%.
OOKP ‐ the Singapore Experience
Authors: WONG D
Published: October 2007

Purpose: The management of severe ocular surface diseases and end‐stage dry eye disorders such as Stevens Johnson syndrome, ocular cicatricial pemphigoid and chemical burns with conventional keratoplasty or keratolimbal allografting remains unsatisfactory. The Osteo‐Odonto Keratoprosthesis (OOKP) is a form of keratoprosthesis (artificial cornea) surgery designed to treat the most severe of these cases, and good outcomes with long‐term retention have been reported. We present the moderate‐term clinical results of Asian patients who have had this device implanted within our Singapore OOKP Program.

Methods: OOKP surgery involves a radical two‐stage procedure – in stage 1, an autologous canine tooth is removed, modified to receive an optical PMMA cylinder, and implanted into the cheek. The entire ocular surface is denuded and replaced with a full thickness buccal mucosal graft. Stage 2 surgery, performed 2‐4 months later, involves retrieval of the tooth‐cylinder complex and implanting it into the cornea, after lifting of the buccal mucosal flap, corneal trephination, iris and lens removal and anterior vitrectomy. Concurrent glaucoma and vitreo‐retinal procedures may also be performed at either stage, if required. Indications for OOKP surgery include bilateral severe blindness, not amenable to keratoplasty or ocular surface transplantation or with previous failed attempts.

Results: In February 2004, the Singapore National Eye Centre embarked on its OOKP program, in collaboration with the National Dental Centre. We have now performed OOKP surgery on 22 patients, with the longest follow‐up being 39 months. Of 16 patients with a mean of 19.1 months follow‐up (range 5‐39 months), no major keratoprosthesis‐related complications have occurred, with full anatomical stability and retention in all cases. 73.3% of patients attained at least 6/12 or better vision, while 90% attained 6/6 vision, and remaining patients have attained, and retained their best visual potential with the exception of one patient who lost vision unrelated to the KPro device (endophthalmitis following glaucoma surgery occurred 1 year after KPro surgery).

Conclusions: OOKP surgery appears to be a highly promising procedure which has the potential to restore excellent vision to the most severe cases of end‐stage corneal disease, when all else has failed. Longer follow‐up of these cases is currently underway.
An update on the AlphaCor
Authors: CRAWFORD G , HICKS C
Published: October 2007

AlphaCor is a new generation of artificial cornea made entirely of pHEMA. It is a flexible 2 part composite device with a transparent centre and a porous skirt, which allows bio‐integration into surrounding host corneal tissue. As a treatment modality AlphaCor exists between traditional keratoprostheses and human donor penetrating keratoplasty. It is most commonly used in high risk corneal regrafts where there is a poor chance of human graft survival.

Data has been obtained on every case of AlphaCor implanted, making it the largest series of keratoprostheses published. With this data and resultant alterations in protocol, there has been a gradual decline in the complication rate for this device. The main complications relate to corneal melting, optic deposition, and posterior inflammatory membranes. Because of the design and technique of implantation, post operative glaucoma is uncommon. The probability of retention at one year is 80% and the visual acuity ranges from PL to 6/6 (20/20). The procedure is “reversible” if necessary so the eye is not lost.

The data indicates that AlphaCor is an effective alternative to donor corneal transplantation in cases at high risk of graft failure. Excellent visual potential and a wide visual field can be obtained.
Validating the Helsinki University Central Hospital (HUCH) working formulation for staging metastatic uveal melanoma
Authors: ESKELIN S , PIPERNO‐NEUMANN S , DESJARDIN L , SCHMITTEL A , BECHRAKIS N , MIDENA E , GRANGE JD , RACT‐MADOUX G , MARSHALL E , DAMATO B , LEYVRAZ S , ZOGRAFOS L , KIVELÄ T
Published: October 2007

Purpose: To validate the Helsinki University Central Hospital (HUCH) Working Formulation, the first substaging system designed to predict prognosis of metastatic uveal melanoma and to facilitate design, reporting and interpretation of controlled clinical trials.

Methods: Data of 226 patients who died of disseminated uveal melanoma were collected from members of the European Ophthalmic Oncology Group (OOG). Karnofsky or WHO performance status, largest diameter of largest metastasis and serum alkaline phosphatase (AP) level at diagnosis of metastases, and time to death were requested. The working formulation is based on a multivariate model that identified these variables as independent predictors of survival, modeling time on chemotherapy as a confounding variable (Eskelin et al. Cancer 2003; 97: 65–75). Patients whose predicted survival was less than 6 months were assigned to stage IVc, between 6 and 12 months to stage IVb and over 12 months to stage IVa. Observed survival time was calculated for each stage.

Results: The median AP level was 0.69 (range, 0.24‐11) times upper normal limit, median largest metastasis was 3.5 cm (range, 0.8‐19), and percentage of patients representing WHO performance index 0, 1‐2 and 3 was 61%, 38% and 1%, respectively. Of the 226 patients, 100 (44%) were assigned to stage IVa, 97 (43%) to IVb and 29 (13%) to IVc. The median observed survival times were 18.3, 10.0 and 4.6 months, respectively. In Kaplan‐Meier analysis, the stages reflected best to worst survival (P<0.0001, log‐rank test for trend).

Conclusions: The collaborative OOG study confirms the HUCH Working Formulation as a repeatable, valid system for dividing patients with metastatic uveal melanoma into groups of differing prognosis.
Where are we with the supra‐Descemetic KPro (Keralia)?
Authors: LAMAR PD , ALFONSO E , STOIBER J , FERNANDEZ V , KAMINSKI S , LACOMBE E , DUCHESNE B , ACOSTA C , PAREL JM
Published: October 2007

Purpose: To assess a non‐perforating supraDescemetic synthetic cornea (Keralia) in rabbits and patients.

Methods: Over 100 rabbits and 20 human cadaver eyes received a sDSC made of 4 polymers, intrastromally (~90% depth) in 59 rabbits, on denuded DM in 17 rabbits, and in a 3rd group (15 rabbits), ~45 days after the application of 1‐heptanol and limbus surgical removal. The corneal surface was covered with a conjunctiva‐Tenon flap trephined ~63 days in postop. 9 last resort cases received a Keralia over the span of 5 years.

Results: sDSC implanted in deep stroma developed opacities in the DM‐KPro optic interface while it rarely occurred with a sDSC placed directly on DM. In burned eyes, 5 animals needed conjunctival flap repair. No eyes had epithelium downgrowth. The Eye Bank eye experiment confirmed implantation to be feasible even in cases of microperforation (3 eyes) but not with macroperforation (1 eye). Histological evaluation displayed a very thin layer of stroma (<2um) remaining on DM in 5 eyes and a minimally thin layer (<10μm) in the others. Of the 9 Keralia, 8 implanted in patients having had multiple PKs, other KPros or previous extensive surgery extruded between 3 months and 1 year while one Keralia implanted in a case of decompensation not amenable to PK remains in place at >2 years.

Conclusions: The supraDescemetic Synthetic Corneas made of HEMA‐MMA34 showed promising results. As opening of the anterior chamber is not required, the sDSC theoretically offers less risks and complications than penetrating KPros.

Support: European project BMH4‐CT97‐9507, Florida Lions Eye Bank, Research to Prevent Blindness, FWF Austrian Science Fund, NIH center grant P30‐EY014801; and the Henri and Flore Lesieur Foundation