bluuebunny/crossref_metadata_2025 huggingface dataset:
Red eye multimedia teaching tool
Authors: PETRICEK P , ANDRAS B , HIGAZY M , NEMETH J , PROST ME
Published: September 2008

Purpose Since 2004, the Eastern Europe and Middle Eastern External Eye Disease Group has been actively involved in creating various educational programs and tools, targeted at general medical public as well as at ophthalmology residents, younger ophthalmologists and family medicine specialists, regarding diagnosis and treatment of various external eye diseases.

Methods The Eastern Europe and Middle Eastern External Eye Disease Group has designed new computer‐based Red Eye Multimedia Teaching Tool, which uses interactive approach, thus enabling active participation of students in teaching process.

Results Red Eye Multimedia Teaching Tool focuses on training in establishing correct diagnosis, as well as choosing the most appropriate therapy for the most common external eye diseases: bacterial, viral and allergic conjunctivitis, as well as dry eye.

Conclusion The newest multimedia teaching tool focuses on diagnosis and treatment of most common external eye diseases, namely bacterial, viral and allergic conjunctivitis, as well as at dry eye. Its interactive approach enables each student to tailor the teaching process to its needs, interests and level of previous knowledge. It is expected to be used by ophthalmology residents, as well as family medicine physicians and other interested medical staff.
Intravitreal injection of bevacizumab to treat choroidal neovascularization with large submacular hemorrhage secondary to age‐related macular degeneration
Authors: DI STEFANO G , IACONO P , BATTAGLIA PARODI M , RAVALICO G
Published: September 2008

Purpose To assess the effects of the intravitreal injection of Bevacizumab (Avastin) to treat choroideal neovascularization (CNV) associated with large submacular hemorrhage (LSH) secondary to age‐related macular degeneration (AMD).

Methods Prospective interventional case series. Patients presenting occult subfoveal CNV with LSH greater the 50% of the entire lesion were recruited. The protocol required 3 monthly consecutive injections, followed by possible repeat injections on the basis of the morpho‐functional responses related to OCT parameters, angiographic features and visual acuity over a 12‐month follow‐up.

Results Eight patients were enrolled in the study and prospectively followed up. Mean visual acuity and mean foveal thickness (FT) at the baseline were 0.72±0.35 (logMAR±SD) and 296±86µm SD, respectively. At three‐month examination, mean visual acuity improved to 0.46±0.28 and mean FT decreased to 240±105µm SD. At 12‐month examination, mean visual acuity was 0.48±0.32, and mean FT 238±50µm. A progressive resolution of macular bleeding was registered in 7 patients. No side‐effect or complication was registered.

Conclusion Intravitreal bevacizumab can be considered a valuable treatment for subfoveal CNV with LSH secondary to AMD. A randomized clinical trial designed with a greater number of patients and a control group is needed to confirm our preliminary results.
Lutein supplementation ‐ the rationale
Authors: NOLAN JM , LOANE E , LOUGHMAN J , BEATTY S
Published: September 2008

Purpose Photo‐oxidation is believed to play a role in age‐related macular degeneration (AMD). Macular pigment (MP), consisting of lutein (L), zeaxanthin (Z) and meso‐Z, protects the retina from photo‐oxidative damage. We review this rationale and critically appraise the current evidence‐base germane to the use of supplements containing the macular carotenoids in patients with, or at risk of developing, AMD.

Methods The evidence supporting a role for MP in the prevention of AMD is primarily available from observational studies and interventional (supplementation) studies. We present data from the following observational and interventional studies: Age‐Related Eye Disease Study (AREDS, I and II); Lutein Antioxidant Supplementation Trial (LAST); LUtein Nutrition effects measured by Autofluorescence (LUNA); Carotenoids in Age‐Related MAculopathy (CARMA).

Results The AREDS I demonstrated that patients with AMD exhibited a 25% risk reduction in progression to advanced AMD when supplemented with zinc plus antioxidants. The LAST reported that visual function improved with L supplementation alone, or with L supplementation in combination with other antioxidants. The LUNA study reported a significant increase in MP optical density with 12 mg L and 1 mg Z, combined with co‐antioxidants (p > 0.05).

Conclusion In conclusion, we await the outcomes of several randomized controlled trials before a truly meaningful comment can be made upon the potential beneficial effects of supplemental L, Z and meso‐Z in patients with AMD. However, the benefits of the macular carotenoids, if any, relate to the ability of these compounds to protect against chronic and cumulative retinal damage and, therefore, the putative protective effect of this pigment may need to be exerted in the young and middle age.
Lutein supplementation ‐ the mechanisms
Authors: WELGE‐LUSSEN U
Published: September 2008

Lutein and zeaxanthin are responsible for the formation of the macular pigment. There is a decrease of macular pigment density with increasing age. There are several studies showing that loss of macular pigment density is associated with an increased risk of age related macular degeneration (AMD). Therefore macular pigment density seems to have a protective effect of the macular from developing AMD. The best characterized role of lutein/zeaxanthin in the protection is the ability to absorb damaging blue light. Furthermore it is known from several in vitro and chemical investigations that lutein/zeaxanthin have anitoxidative properties. Based on the fact, that oxidative plays a major role in the pathogenesis, lutein/zeaxanthin could also protect the macular from damaging free radicals. A natural response of oxidative stress is the process of inflammation. Based on genetic studies and morphological studies AMD revealed the involvement of a subclinical inflammation in AMD pathogenesis. Lutein/zexaxanthin have anti‐inflammatory properties. This fact may explain the recently described inhibition of choridal neovascularisation in an experimental model of wet form of AMD. Taken together lutein/zexaxanthin are ideal candidates to protect the macular from damaging blue light, oxidative stress and subclinical inflammation. Based on these findings lutein/zeaxanthin seem to be ideal substance to prevent and stop progression of AMD.
Reducing mitochondrial dysfunction and ganglion cell death: focus on use of α‐lipoic acid
Authors: OSBORNE NN
Published: September 2008

Purpose Retinal ganglion cell axons within the globe enriched with mitochondria. Good evidence exists to suggest that when mitochondria are drastically impaired as might occur in retinal ischemia or glaucoma, ganglion cell apoptosis occurs. Thus agents targeted specifically at enhancing ganglion cell mitochondrial energy production and/or scavenge free radicals (known to be generated by dysfunctional mitochondria) might therefore be useful to treat a disease like glaucoma. One such substance is possibly α‐lipoic acid.

Methods Rats were injected intraperitoneally with either vehicle or α‐lipoic acid (100 mg/kg) once daily for 11 days. On the 3rd day, ischemia was delivered to the rat retina by raising the intraocular pressure above systolic blood pressure for 45 min. The electroretinogram was measured prior to ischemia and 5 days after reperfusion. Rats were killed 5 or 8 days after reperfusion and the retinas were processed for immunohistochemistry and for determination of mRNA levels by RT‐PCR. Insults were also delivered to retinal cells in culture (anoxia, light) and the influence of α‐lipoic acid examined.

Results Ischemia‐reperfusion affected the electroretinogram and caused a decrease in nitric oxide synthase and Thy‐1 immunoreactivities and retinal ganglion cell‐specific mRNAs. Exposure of retinal cells to light or anoxia caused a loss of cell viability. α‐Lipoic acid attenuated all these effects.

Conclusion The results show that α‐lipoic acid provides protection to the retina and their ganglion cells from ischemia‐reperfusion injuries. It also blunts any loss of retinal neurons in culture caused by anoxia or light. Since α‐lipoic acid can be tolerated when taken orally its use for treating e.g. glaucoma is worthy of consideration.
Intravitreal bevacizumab (Avastin) treatment in neovascular age‐related macular degeneration: 6 months results
Authors: CIMBALAS A , BAGDONIENE R , SIRTAUTIENE R , LIVEIKIENE A , ASOKLIS R
Published: September 2008

Purpose To study the visual and anatomic outcome of the intravitreal bevacizumab injection in the treatment of neovascular age‐related macular degeneration (AMD).

Methods 86 eyes of 79 patients (mean age: 74.9) who received one or more intravitreal bevacizumab injections for neovascular AMD and had a follow‐up of at least 6 months were analyzed retrospectively. Visual acuity (VA), optical coherence tomography (OCT) macular thickness,pretreatments and number of the needed treatments were evaluated.

Results Results showed a mean visual acuity of 0.14 before the first intravitreal injection with bevacizumab. Six months after the first injection, patients VA increased by 0.18, i.e. they gain 0.04 lines of Snellen (P = 0,003). The mean number of treatments needed at this time was 3.3 (range: 1 to 5 injections). Central retinal thickness (CTR) assessed with OCT was 354±187 µm before the first treatment and decreased by 150±169 µm after 6 months (P < 0,001). 14% of the patients needed a treatment at the 6‐months follow‐up. One patient presented uveitis several days following intravitreal injection of bevacizumab.

Conclusion Six months follow‐up of the intravitreal bevacizumab in the eyes with neovascular AMD showed stabilization of the visual acuity.
Spherical equivalent versus AL/CR ratio ‐ a tool for classifying refractive error
Authors: MORGAN IG , ROSE KA
Published: September 2008

Purpose To demonstrate that refractive development in children can be analysed in terms of three phases of development, defined in plots of cycloplegic spherical equivalent refraction (SER) versus the ratio of the axial length to the corneal radius (AL/CR ratio), rather than as a unitary process of emmetropisation.

Methods Schools were randomly selected, with stratification by SES. Partipation was sought from students in Year 3 (age 6‐7) and Year 7 (age 12‐13). Participation was high (>75%). Cycloplegic SER (autorefraction), AL and CR (IOL Master) and height were measured in over 4000 children, giving two representative cross‐sectional samples.

Results Plots of SER versus AL/CR ratio were triphasic, consisting of a hyperopic wing (SER >2D, an internediate sone (SER between ~0‐0.5D and 2D) and a myopic wing (SER <0‐0.5D) The relationship between differences in SER and AL changed between the phases (>2D/mm in hyperopic and myopic wings, but <1D/mm in the the intermediate zone). Correlations between SER, AL and height decreased across the three phases.

Conclusion We interpret these plots as defining a developmental trajectory for refractive development. In the first year of life, rapid adjustment of AL to CR produces leptokurtic distributions of SER and AL/CR, at mildly hyperopic mean SER. Children with SER >2D after the first few years of life may be unable to emmetropise. The impact of continuing increases in AL on SER is reduced by compensatory reductions in lens power, in an anti‐emmetropic phase. For SER of <~0‐+0.5D, lens power changes cease, and further AL increases lead to myopia. The utility of analysis in terms of these phases is illustrated by the systematic changes in relationships between SER, AL and height. This analysis may have wider application.
The measurement of light intensities and effects on myopia development
Authors: ROSE KA
Published: September 2008

Purpose Given the protective effects of time spent outside against the development of myopia, the aim is to outline methods for assessing time spent outside and light exposures in population studies of the risk factors for myopia.

Methods The questionnaire previously used in the Sydney Myopia Study was used as the basis for further refinement, by a WHO working group; Kathryn Rose (Australia), Seang‐Mei Saw (Singapore), Terri Young (USA, Singapore), Mingguang He (China), Jane Gwiazda (USA), Yuddha Dhoj Sapkota(Nepal), Solange R. Salomão(Brazil) and Leon Ellwein (USA). The questionnaire was field‐tested at several sites. Light intensities at a variety of indoor and outdoor locations were sampled to predicted location during daylight hours.

Results Protection from myopia is associated with time spent outdoors, irrespective of whether sport was engaged in, and indoor sport is not protective. The existing questionnaire was therefore simplified to include questions which directly addressed the issue of how much time was spent outside and inside during daylight hours. Measurements of the light intensity at various indoor and outdoor locations showed that light intensity during daylight hours had high specificity and selectivity for estimating location. These measurements also showed that light intensities encountered during travel to and from schools were variable depending on the children walked or cycled, or traveled by train, bus or car. The questionnaire was modified to cover this issue.

Conclusion The development of a standard questionnaire for studies of time spent outdoors and the aetiology of myopia will facilitate international comparison of data. It is recommended that comparable information on ambient light intensities also be collected.
Cornea biomechanical characteristics measured using the Ocular Response Analyzer in Singapore children
Authors: LIM LS , GAZZARD G , CHAN Y , FONG A , KOTECHA A , SIM E , TAN D , TONG L , SAW SM
Published: September 2008

Purpose To determine the corneal biomechanical parameters measured with the Reichert Ocular Response Analyser(ORA) in Singaporean children, and to assess their correlations with refractive error and biometry

Methods This was a cross sectional study of 271 subjects from the Singapore Cohort Study of Risk Factors for Myopia(SCORM). Corneal hysteresis (CH), corneal resistance factor(CRF), central corneal thickness(CCT) and intraocular pressure(IOPcc) were measured with the ORA. Spherical equivalent refraction, axial length, height, weight, and blood pressure were measured.

Results The mean age of the study population was 13.97±0.89years, the gender distribution was almost equal(138 males,50.9%),and the majority were Chinese.The mean CH and CRF were 11.78±1.55mmHg and 11.81±1.71mmHg. CH and CRF did not vary with age, sex or race. CH and CRF did not vary with myopia (p=0.79;0.83), or axial length (r=‐0.11 and ‐0.05,p=0.08 and 0.40). Multivariate analyses were performed with CH, CRF or CCT as the dependent and age, gender, race, weight, IOPcc, CCT, SE refraction, and corneal curvature as covariates. CH was significantly associated with IOP (beta=‐0.22(95%CI ‐0.27,‐0.17)), CCT (beta=0.03(0.02,0.03)) and corneal curvature (beta=‐1.13(‐2.08,‐0.19)). CRF was significantly associated with IOP, CCT and corneal curvature.(beta=0.08(0.02,0.14);0.03(0.03,0.04) and ‐1.39(‐2.54,‐0.23) respectively). The only factor predictive of decreased CCT was Malay or Indian race compared with Chinese.

Conclusion The CH and CRF values in our study on children are slightly higher than in adult studies. CH and CRF are not associated with refractive error or axial length. Flatter corneas are associated with lower CH and CRF readings
Efficacy of pegaptanib sodium in occult or minimally classic
Authors: ZOURDANI A , HADDAD W , SOUIED E , COSCAS G , SOUBRANE G
Published: September 2008

Purpose Recent studies have highlighted the efficacy of Pegatanib sodium in sub‐epithelial, occult, CNV seen in the early stages of the disease.

Methods This was a prospective study with a follow‐up of 24 months. Patients underwent a complete examination including ETDRS visual acuity measurements, fundus photographs, FA and ICG‐A and OCT, as well as treatment by intra‐vitreous injection every 6 weeks.

Results 24 patients (16 women) presenting with exudative ARMD were chosen. The mean age was 76 years. 8 eyes had a sub‐epithelial occult without classic neovascular lesion, or minimally classic. 8 eyes had a neovascular lesion of pre‐epithelial type, predominantly classic. 4 eyes had a neovascular lesion of chorio‐retinal anastomosis (CRA) associated with a PED. 4 lesions were fibro‐vascular in type. At the end of the study, 100% of pure, occult type or « minimally classic » lesions presented with a loss of less than 15 letters of VA and in 25% of cases there was an improvement of 15 letters or more. Six out of eight treated patients did not lose any letter and five patients had an improvement of at least one letter. These patients had an initial VA of 20/100 or more. FA did not demonstrate any leakage in six cases, and OCT demonstrated an absence of intra‐retinal edema in all cases. Out of the 16 patients who presented with a « predominantly classic » or with CRA or with fibro‐vascular type lesion, only 3 had an improvement of at least one letter compared with 10 who had the loss of more than 15 letters of VA. Patients in younger age brackets had the better functional results.

Conclusion Treatment with Pegaptanib sodium is indicated preferentially for occult or minimally classic type lesions, which are recent and small.
An unusual lid/orbital tumour in infants
Authors: IRION LD , BONSHEK R , LEATHERBARROW B , BHATT P , MCCORMICK A
Published: September 2008

Purpose To present 3 cases of an unusual soft tissue lesion in infants with clinicopathological correlation.

Methods Case 1: A 2‐year‐old boy presented with a rapid growing lesion in his right lateral orbit. Case 2: A 5‐year‐old girl with a left superior orbital lesion close to lacrimal sac. Both cases had clinical appearances of a dermoid and excision was performed. Case 3: A 1‐year‐old boy presented with a 6 week history of an enlarging right medial canthal mass. CT scan showed a greatly expanded nasolacrimal duct. Endoscopy revealed a polypoid lesion and multiple biopsies were taken.

Results The specimens from cases 1 and 2 consisted of firm nodular tissue measuring up to 30 and 18mm in diameter respectively. Several biopsies (2‐6mm) were submitted from case 3. In all cases histology showed plump spindle cells arranged in interweaving fascicles in a collagenous stroma. Variable amount of myxoid change was present. There was no necrosis or mitotic activity. Diffuse SMA and focal CD68 positivity were encountered. Negative markers were: CD34, S100, neurofilament, desmin, MyoD1 and myogenin. The overall features were those of a nodular fasciitis.

Conclusion Only four cases of orbital nodular fasciitis have been reported in children younger than 5 years. We report a series of further three cases in this age group, two masquerading as a dermoid, raising the awareness of this entity as a clinical differential diagnosis of rapidly growing lid/orbital lesions in infants.
No functional vision improvement after intravitreal ranibizumab injections (IVT) for retrofoveolarchoroidal neovascular age‐related macular degeneration, why?
Authors: GONZALEZ C
Published: September 2008

Purpose To analyse the reasons of no improved functional vision in retrofoveolar choroidal neovascular AMD treated with ranibizumab IVT.

Methods 95 eyes of 80 patients,21 men,59 women,with retrofoveolar choroidal neovascular AMD treated by ranibizamab IVT.57 were inaugural cases ,38 previously treated by phototherapy and/or pegaptanib IVT.Patients received intravitreal ranibizumab injection,3 times,every 4 weeks in an inductive treatment,the next injections depending on the follow‐up results.First and 2 months’ interval follow‐up exam included ETDRS visual acuity (VA),complete ophthalmic examination,fundus autofluorescence(FAF),fluorescein (FA) and infracyanine (ICG) angiography,and time and/or spectral domain optical coherence tomography (OCT).VA and OCT were done before each IVT.FAF,OCT,FA and ICG analysis appreciate photoreceptor(PR),pigment epithelium(PE) layers,atrophic areas,neovascular net’s leakage and flow.

Results Atrophic areas increased 20%,above all in predominant atrophic areas AMD, photoreceptor layer decreased in depth in 30%,pigment epithelium was 25% less dense in 42%,exudative reaction was 30% still present in 58%,neovascular net’s flow and leakage was 45% left in 60%.Initial intense exudative neovascular AMD, most atrophic PE areas AMD,choroido‐retinal anastomosis with neovascular AMD were predominantly concerned.Results are nevertheless better than PDT alone,than pegaptanib IVT on exudative reaction but obviously no,on PR and PE trophicity.AMD and/or ranibizumab IVT involvement is discussed.

Conclusion To consider all those notions is essential to choose the best therapeutic strategy, the most appropriate selective or no anti‐VEGF, to go on in the understanding of AMD.
Ocular surface and glaucoma therapy
Authors: BROADWAY D
Published: September 2008

Purpose The use of anti‐glaucoma medications is often associated with ocular adverse reactions. These undesirable effects may lead to reduced quality of life, poor adherence or even treatment discontinuation in patients with glaucoma. This presentation summarizes currently available data relating to the effect of topical anti‐glaucoma preparations on the ocular surface.

Results Anti‐glaucoma medications most commonly contain benzalkonium chloride (BAK) as a preservative. In vivo animal studies together with in vitro experiments have demonstrated various dose dependent adverse effects of BAK. Clinical studies have also shown an increased incidence of adverse events associated with BAK and have demonstrated that withdrawal of the preservative reduces these effects.

Conclusion Collectively, these data suggest that use of preservative‐free anti‐glaucoma treatments have clinically relevant benefits for patients.
Overview of the profile of tafluprost
Authors: UUSITALO HMT
Published: September 2008

Purpose Tafluprost (Taflotan®) is a new potent PGF2_ analogue for the treatment of glaucoma. Tafluprost is the first prostaglandin available as a preservative free formulation. This presentation summarizes the pre‐clinical and clinical profile of tafluprost.

Results Tafluprost is a potent and selective FP receptor agonist. It lowers IOP by mainly increasing the uveoscleral outflow. Tafluprost had potent IOP lowering effect in normotensive and ocular hypertensive monkeys, unsurpassed by latanoprost. In healthy volunteers tafluprost was well tolerated, safe and effective in IOP lowering. Based on dose response data 15 micrograms/ml was chosen as the final concentration. This concentration had a comparable IOP lowering effect to latanoprost in P‐II studies. Effective IOP lowering was confirmed in pivotal clinical studies. All adverse effects reported were well known for the prostaglandin analogues. The most frequently reported adverse event was hyperaemia. It was reported in 13% of patients. A preservative free form of tafluprost showed equal efficacy and pharmacokinetics to the preserved form. Preservative free tafluprost has low or no pro‐apoptotic, pronecrotic or pro‐oxidative effects in vitro compared to preservative‐containing prostaglandin formulations latanoprost, travoprost and bimatoprost.

Conclusion Tafluprost (Taflotan®) is a new effective, well tolerated and safe IOP reducing agent. Importantly Tafluprost is the first prostaglandin analogue commercially available as preservative‐free formulation. There is a growing body of evidence that this has a clinical relevance in the treatment of chronic diseases like glaucoma and especially in patients with dry/sensitive eyes.
Preliminary reading centre concordance in OCT grading in the UK IVAN Study
Authors: PATTON WP , MULDREW KA , PETO T , LENFESTY P , HARDING SP , CHAKRAVARTHY U
Published: September 2008

Purpose To report on concordance of optical coherence tomography (OCT) grading in the Network of Ophthalmic Reading Centres UK (NetwORC UK). The present study looks at concordance of OCT gradings across the network for patients enrolled in the UK IVAN Study.

Methods A set of 5 patient scans (6 radial line scans and one 7mm offset scan using the Stratus OCT III (Zeiss, UK)) were graded by accredited graders at all three centres. Scans were exported as JPEG images with a corresponding PDF. Measurements for the Outer High Reflectivity Band (OHRB), Sub Retinal Fluid (SRF), Pigment Epithelial Detachment (PED), maximum height of largest cyst, maximum retinal thickenss (MRT) and foveal retinal thickness (FRT) were taken, if present.

Results In all cases an acceptable level of concordance was achieved. One case proved more problematic than the others and results were more varied. For OHRB, SRF, PED, cyst, MRT and FRT the measurements by individual graders were consistent in 4 out of 5 cases. One case showed wider‐ranging measurements with the range for OHRB varying by 0.25mm (mean thickness 0.22mm).

Conclusion The present study shows an acceptable level of concordance for OCT grading across NetwORC UK. In difficult cases, the complexity of AMD grading explained the lack of total concordance when an abnormal thickening of the OHRB is present. The most problematic case had an area of moderate hyperreflectivity anterior to the OHRB which caused difficulty and highlighted a specific area for further training and a protocol amendment. The exercise was useful in highlighting both individual and overall training needs which are currently being addressed in each of the RCs. The concordance study is being extended to include a larger dataset.
Treatment of myopic neovascularization with ranibizumab
Authors: EGEA ESTOPINAN MC , TORRON C , GUERRI MONCLUS N , BORQUE E , RUIZ O , FERRER E , HONRUBIA FM
Published: September 2008

Purpose To determine the safety and efficacy of ranibizumab, as a treatment of choroidal neovascularization associated with pathological myopia

Methods A retrospective, non‐comparative study of 14 patients treated with injections of intravitreal Ranibizumab. Four patients had been treated before with photodynamic therapy and had not improved visual acuity, whereas the patients treated with ranibizumab improved visual acuity. After a complete ophtalmologic examination, fluorescein angiography (FAG) and optical coherence tomography (OCT) intraocular injection was practised, retreatment was decided according to the subjective impression of the patient, visual acuity, presence or absence of metamorphopsia, biomicroscopy of posterior pole and characteristics of OCT. The patients were included after a minimal follow‐up of 6 months.

Results We analysed 17 eyes of 14 patients. The average age of patients was 56 years. The spherical equivalent average was 13.6 diopters. The initial and final average visual acuity was 0,29 and 0,57 respectively. All neovascular membranes were classified as classical and localized sub or yuxtafoveal. Visual acuity improved or remained stable in all eyes. In all cases retinal thickness and macular edema observed in OCT decreased. There were no systemic or ocular complications, one patient responded with macular haemorrhage and decrease in visual acuity after four injections of ranibizumab.

Conclusion The short‐term results of this small study suggest that Ranibizumab may be a good therapeutic option in the treatment of myopic neovascularisation. It improves visual acuity and anatomy, even in patients that don´t respond to photodynamic therapy.
Anti‐PlGF (placental growth factor) as a safer alternative for anti‐VEGF in the treatment of age‐related macular degeneration (AMD)?
Authors: VAN DE VEIRE S , VINORES S , PERIC A , MAZZONE M , MOONS L , CARMELIET P , STALMANS I
Published: September 2008

Purpose To evaluate the efficacy and safety of PlGF blockage by inhibiting choroidal neovascularization (CNV) in a mouse model of AMD.

Methods A laser‐induced CNV model was used in C57Bl/6 mice. Mice were injected intraperitoneally with 25 mg/kg of an anti‐PlGF‐antibody, an anti‐VEGF receptor2 (VEGFR2) antibody, a combination of both, or a control antibody. The CNV lesions were evaluated on flat mounts and serial sections after 14 days, by immunostainings for endothelial and inflammatory cells (CD31 and F4/80 respectively). Ganglion cell survival was scored via NeuN and TUNEL staining after 2, 4, and 6 weeks in C57Bl/6 and Swiss mice with and without CNV lasering. Safety of anti‐PlGF and anti‐VEGFR2 on normal vascular development in the retina, kidney, and heart was assessed.

Results Anti‐PlGF or anti‐VEGFR2 comparably inhibited CNV by ± 50%. Moreover, a combination treatment of the optimal dose of anti‐PlGF and a lower dose of anti‐VEGFR2 further suppressed CNV to ± 70%, allowing to reduce the dose of anti‐VEGFR2 by fourfold. Anti‐PlGF did not inhibit vascular development in the retina, heart, or kidney, whereas a reduction of ± 40% was seen after anti‐VEGFR2 treatment. Repeated anti‐VEGFR2 injections induced an increase in ganglion cell apoptosis after 4 and 6 weeks of administration, whereas anti‐PlGF did not.

Conclusion Anti‐PlGF treatment inhibits CNV formation in a mouse model of AMD, and enhances the efficacy of anti‐VEGFR‐2, allowing the dose of anti‐VEGF therapy to be lowered and the potential adverse effects to be minimized. Moreover and contrary to anti‐VEGFR2, anti‐PlGF is safe for the neuroretina and for the systemic and retinal vascular development.
Analysis of intravitreal ranibizumab injections effects on exudative reaction complicating subfoveal choroidal neovascular age related macular degeneration (AMD)
Authors: GONZALEZ CG
Published: September 2008

Purpose To evaluate the effect of RANIBIZUMAB intravitreal injections(IVT) on exudative reaction secondary to retrofoveolar neovascular AMD,at short and long term evolution

Methods 110 eyes of 88 patients , 31 men,57 women, with retrofoveolar sub‐retinal neovascularisation complicating AMD .65 were inaugural cases,23 previously treated by photodynamic therapy and/ or pegaptanib IVT. Patients received intravitreal ranibizumab injection, 3 times, every 4 weeks in an inductive treatment, the next injections depending on the follow‐up results. First and 2 months’ interval follow‐up exam included ETDRS visual acuity (VA), complete ophthalmic examination, fluorescein (FA) and infracyanine (ICG) angiography, and optical coherence tomography (OCT).VA and OCT were done before each IVT.OCT was evaluated and compared time to time and cut to cut, FA and ICG analysis appreciate neovascular net’s leakage and flow.

Results Exudation decreased intensely in all cases.Diffuse oedema was 70% reduced in 80% cases,cystoid oedema was 75% less in 65%, retinal serous detachment was 80% decreased in 78%.Angiographic leakage reduced about 70% in 72%.At ICG ,vascular flow wAS 2/3 time less in 55%. Best results noted than with PDT alone and/or pegaptanib IVT, and with no anastomosis lesions. Exudation scale was considered, compared with FA and ICG follow‐up results and for next IVT criteria and indications. Inductive treatment was sufficient in 74 cases.

Conclusion The results, with indeed reduction of exudation on OCT, lack of fluorescein leakage, low neovascularisation’s flow in ICG, suggest Ranibizumab IVT seem effective on exudative neovascular reaction complicating AMD and OCT be the main evaluation means.
Photodynamic therapy for choroidal neovascularization secondary to choroidal nevi
Authors: GAMBRELLE J , MAUGET FAYSSE M , QUARANTA EL MAFTOUHI M , GRANGE JD
Published: September 2008

Purpose To assess the efficacy and the safety of photodynamic therapy (PDT) for treatment of choroidal neovascularization linked to choroidal nevi.

Methods It is a retrospective study including choroidal neovascularization secondary to choroidal nevi treated by PDT for 1999 to 2005. PDT was performed according to the standard protocol used for treating choroidal neovascularization secondary to age‐related macular degeneration (ARMD). Post‐PDT follow‐up was also done according to the guidelines used in ARMD. Moreover, tumors were controlled every 3 months.

Results Six choroidal neovascularizations secondary to choroidal nevi were included in our study. All nevi were localized in the posterior choroids. The median of their largest diameter was of 3mm and their thickness was <2mm in all cases. Neovascular membranes were “classic” in all cases, subfoveal in 2 cases, juxtafoveal in 3 cases and extrafoveal in 1 case. The sizes of choroidal neovascularization were ≤ 1‐disk‐diameter in half the cases. On average 3.3 sessions of PDT were necessary to obtain the stabilization of choroidal neoascularization. The mean follow‐up was 35 months without any patient lost of follow‐up. Visual outcomes were extremely variable. Large or retrofoveal choroidal neovascularization but also antecedents of atrophic ARMD were related with worse functional results. No growth of the nevi was observed.

Conclusion Choroidal neovascularization is considered to be a relative indicator of benignity of the naevus. However, it often marks a definitive turning point in the visual function. PDT appears as a safe and efficient procedure for treating choroidal neovascularization secondary to choroidal naevus with results similar to those observed in ARMD.
RNase‐7 expression mediated by IL‐1 beta in human ocular surface cells via multiple signalling pathways
Authors: MOHAMMED I , ABEDIN A , HOPKINSON A , DUA HS
Published: September 2008

Purpose Antimicrobial peptides are known to play an essential role in the host defense system. It was recently identified that the Ribonuclease(RNase)‐7 posses a broad‐spectrum microbicidal property against various pathogens.In this study our aims were a)to investigate the RNase‐7 expression in ocular inflammation and/or infection and b)to identify the involvement of possible signalling pathways in interleukin(IL)1‐beta mediated RNase‐7 expression using SV40‐immortalised human corneal epithelial cell line(SHCEL).

Methods a)Total RNA was obtained from impression cytology specimen of normals and diseased individuals. Quantitative polymerase chain reaction technique was used to analyze RNase‐7 mRNA expression. b)SHCELs were treated with IL‐1beta and inhibitors of signalling molecules both in time‐ and dose‐dependent manner.Quantitation of both phosphorylated and total proteins was evaluated using Western blotting. The effect of IL‐1beta and inhibitors on secretory cytokines in SHCELs was measured using BD‐cytometric bead arrays.

Results The normalised expression of RNase‐7 mRNA significantly increased in disease conditions (bacterial, viral, dry‐eye and acanthamoeba keratitis). Inhibition of following signalling pathways: PI3K(phosphatidylinositol‐3‐kinase), MAPK(mitogen‐activated protein kinase) and NF‐kB(nuclear factor‐kB) have reduced the RNase‐7 gene expression. Significant changes in the secreted cytokines (IL‐6, ‐8, ‐10 and‐12p70) was also demonstrated.

Conclusion The first study which demonstrates the RNase‐7 expression in the eye. The involvement of multiple signalling pathways in RNase‐7 induction by IL‐1beta may facilitate the development of novel approaches in enhancing antimicrobial defense and healing of the eye.
Expression pattern of antimicrobial peptides (AMPs) in acanthamoeba keratitis
Authors: OTRI AM , ABEDIN A , MOHAMMED I , PANJWANI N , HOPKINSON A , DUA HS
Published: September 2008

Purpose Acanthamoeba keratitis (AK) is a sight‐threatening ocular infection, which is more likely in contact lens wearer. Antimicrobial peptides(AMPs)are cationic polypeptides with wide‐spectrum activity against pathogens. We studied(1)the profile of AMP mRNA expression in ex‐vivo impression cytology (IC) specimen from normals and 5 AK patients &(2)compared AMP gene expression between ex‐vivo and in‐vitro cell culture samples.

Methods a) IC samples were collected for Total RNA extraction and cDNA synthesis. Quantitative gene expression(qPCR)was employed to evaluate expression of Defensins,Cathelicidin,& Liver‐expressed AMPs (LEAPs).b) Immortalised human corneal epithelial cell line (HuCL) was incubated with trophozoites of Acanthamoeba castellanii for 24 hours and the supernatant analysed by BD cytometric bead array for pro‐inflammatory cytokines.The cells were processed for qPCR analyses.

Results Variable expression of AMPs was observed in AK patients.Eight AMPs,Human Beta defensins(HBD)1 to 3,Cathelicidin (LL37,LEAP 1 and 2 and DEF 109 were detected.Of these HBD 1 to 3 and DEF 109 were shown to be reduced and whereas LEAP 1 & 2 were induced in AK specimen. Similarly, increased mRNA expression of LEAP 1 & 2 was also demonstrated in Acanthamoebae treated HuCL cultures.Whereas, HBDs showed the baseline expression when compare to untreated HuCLs.

Conclusion This is a first study demonstrating AMP gene expression in AK. Differential expression pattern of these AMPs during AK may have important implications in understanding the pathogenesis of this blinding infection. Modulation of AMP defense barrier at the ocular surface or use of the AMP as a contact lens preservative agent may help to reduce the AK infections
Profile of antimicrobial peptides (AMPs) at the ocular surface
Authors: ABEDIN A , OTRI M , MOHAMMED I , HOPKINSON A , DUA HS
Published: September 2008

Purpose Purpose: Antimicrobial peptides are eukaryotic analogues of antibiotics and serve as early effectors of innate defence. Our aim was to profile the spectrum of AMPs at the ocular surface in health and disease.

Methods Methods: Reverse Transcription‐Polymerase Chain Reaction (RT‐PCR) and real time PCR techniques with primers for 21 known AMPs were employed to evaluate gene expression on the following human ocular surface (OS) samples: a) Impression cytology specimen of normals and patients suffering from bacterial, viral keratitis and acanthamoeba keratitis and dry eyes. b) OS cells from cadaver donors and c) cultured corneal epithelial cells from limbal explants. Over one hundred samples were thus studied.

Results Results: AMP expression was observed in all the different groups of samples but was variable. Nine AMPs, namely Human Beta defensins (HBD) 1 to 4, Cathelicidin (LL37), Liver expressed antimicrobial peptides, LEAP‐1 and ‐2, DEFB‐109 and RNAse were detected. Of these, HBD3 was prominent in bacterial keratitis and LEAP 1 and LL37 in viral keratitis. LEAP 2 and LL37 showed an increased tendency of expression in dry eyes. DEFB‐109 was the only AMP found to show decreased expression in the inflammatory conditions studied. RNAse, the most potent of all AMPs was found in abundance at the OS.

Conclusion Conclusions: The OS is endowed with a range of AMPs which contribute to defence against environmental microbes and also participate in other immune mediated, inflammatory and wound healing events. They hold promise as therapeutic agents against microbes and in modulation of inflammation and wound healing.
Microbiological culture and panbacterial PCR yield of diluted or undiluted vitreous from vitrectomy are comparable in acute postsurgery endophthalmitis (FRIENDS group)
Authors: CHIQUET C , VINH MOREAU GAUDRY V , CORNUT PL , CREUZOT CP , THURET G , DENIS P , MAURIN M , VANDENESCH F , BRON AM , PECHINOT A , ROMANET JP
Published: September 2008

Purpose To compare the diagnostic yield of microbiological analysis performed on diluted and undiluted vitreous samples from pars plana vitrectomy in patients with acute postcataract surgery endophthalmitis.

Methods Undiluted and diluted vitreous samples were harvested in 34 patients at the beginning of the vitrectomy, among the 57 vitrectomized patients (out of 100 patients presenting with an acute postcataract surgery endophthalmitis) included in the multicenter prospective study FRIENDS (2004‐2005). Vitrectomy was performed after one (n=12) or two (n=22) antibiotics intravitreal injections. Each vitreous sample was divided into two parts for conventional culture (Brain Heart Infusion broth) and panbacterial PCR, respectively.

Results Microbiological analysis of both undiluted and diluted vitreous allowed a bacterial identification in 28 out of 34 cases (82.3%). Microbiological diagnosis using undiluted vitreous and conventional culture was negative in 32 cases and positive in 2 cases. In one case, there was a discrepancy between undiluted (culture negative) and diluted vitreous (S. epidermidis). Analysis of both undiluted and diluted vitreous using PCR was positive in 28 cases and negative in 6/34 cases. There was a discrepancy between both samples in three cases.

Conclusion Microbiological results combining PCR and cultures showed that diluted vitreous analysis may replace analysis of undiluted vitreous. The diluted sampling of vitreous, more easily performed and less iatrogenic, may be recommended when panbacterial PCR is used .
Neovascular AMD; Effect of intravitreal ranibizumab on the retinal arteries
Authors: PAPADOPOULOU DN , MANGIORIS GF , MENDRINOS E , DONATI G , POURNARAS CJ
Published: September 2008

Purpose To study the effect of intravitreal injection of ranibizumab on the retinal arteries’ diameter in patients with neovascular age‐related macular degeneration

Methods Five patients with new‐onset neovascular age‐related macular degeneration were evaluated. All patients had three monthly administrated intravitreal injections of ranibizumab. The diameter of the retinal arteries was measured in vivo with a Retinal Vessel Analyzer (RVA). The measurements were performed before the first intravitreal injection and at days 7 and 30 after the first, the second and the third injection. Blood pressure was also monitored at the same time‐points.

Results No significant change on the retinal arterial diameter was observed after the first injection and 7 days after the second injection when compared to baseline; mean decrease in retinal arterial diameter was 1.64% and 3.5% respectively. A significant vasoconstriction of the retinal arteries was observed thereafter. Thirty days following the second and third injection, there was a mean decrease of 12.4% and 17.8% respectively on the retinal arterial diameter compared to baseline values (p < 0.05). There was no significant change in mean arterial systolic or diastolic blood pressure during the period of follow‐up.

Conclusion These results suggest that intravitreal ranibizumab induces retinal vasoconstriction in patients with neovascular age‐related macular degeneration following the second injection. Further studies with larger sample sizes are needed to confirm these results as well as its potential adverse effects in the retinal circulation in patients with age‐related macular degeneration and with other retinal vascular diseases.
Developing a recovery psychological model for patients undergoing KPro surgery
Authors: BUSUTTIL A , LIU C
Published: September 2008

Undergoing keratoprosthesis surgery is demanding Physically, Psychologically and Socially. Good outcomes, including improving Quality of Life, require that all these domains are considered during patient selection, surgery and during follow up. Evaluation of Psychosocial outcomes after medical events often limit themselves to areas such as Anxiety and Depression using an illness model rather than a Recovery Model, using quantitative rather than qualitative methodology, and thereby possibly limiting the information received and which could potentially be used to help patients adapt and cope. The Brighton OOKP service seeks to integrate patient experience to inform a Bio‐psycho‐social approach using Qualitative methodology to complement earlier quantitative work undertaken in the service. Integrating this information with the experience of the specialised clinical team and the wider literature in areas such as Resilience, Coping, and Social Support and drawing on the literature on sight loss/recovery and living with changed appearance will contribute to the emergence of a Recovery Model for OOKP patients. This approach looks at processes which support or impede recovery and seeks to act upon them. Through this it is envisaged that the service will be better able to support patients as they consider, experience and live with a KPro such as the OOKP. This presentation will discuss progress to date.
More than 50 years of experience with keratoprostheses
Authors: BARRAQUER J
Published: September 2008

We started to use acrylic corneal prostheses experimentally in 1955, principally in eyes considered functionally lost or after several attempts of other keratoplastic procedures had failed. In our first 15 cases a Dorzee prosthesis or a modified Dorzee prosthesis (Barraquer‐Cardona) had been used, in three cases some useful vision was obtained for several months or even up to 4 years. However, the expulsion rate was high, mainly due to the lysis of the corneal borders around the prosthesis. The communication of Strampelli’s first technique of osteo‐odonto‐keratoprosthesis, using a “live” support encouraged us to continue our experimentation. A case of bilateral blindness in a 50 year old patient, due to mine explosion in 1941 (Second World War) was first seen in 1965, 25 years after the accident. The right eye was lost due to retinal detachment, the left eye was aphakic, with opaque cornea due to explosion impacts and anterior synechiae due to old perforations. In 1965 osteo‐odonto‐keratoprosthesis, using Strampelli’s first technique, was performed with good recuperation of vision (0.4) for 10 years. Different aspects and details of the case are presented and commented. Unfortunately in 1975 necrosis of the bone support developed and reconstructive keratoplasty had to be performed. The patient remained with very low visual acuity (0.03) and a very reduced visual field. The author considers that this result, obtained with the very limited facilities available more than 40 years ago, confirms and justifies that experimentation in this field must continue, making use of all technological, surgical, pharmacological and research facilities available today.
Association between flicker‐induced vasodilatation and flow mediated vasodilatation in patients with diabetes, systemic hypertension and hypercholesterolemia
Authors: GARHOFER G , PEMP B , PETZL U , WOLZT M , SCHMETTERER L
Published: September 2008

Purpose Flicker induced vasodilatation is reduced in patients with vascular related diseases. However, the reason for this diminished response is unclear, but may be related to endothelial dysfunction. Currently, the standard method to assess endothelial function in vivo is flow mediated vasodilatation (FMD). Thus, the present study was performed to investigate whether a correlation exists between flicker induced vasodilatation and FMD in patients with diabetes and patients with mild systemic hypertension and/or hypercholesteremia.

Methods In the present study 20 patients with insulin dependent diabetes, 40 patients with systemic hypertension (systolic blood pressure:140‐159 mmHg; diastolic blood pressure 90‐99 mmHg) and/or serum cholesterol plasma levels > 250 mg/dl and 20 healthy control subjects were included. The flicker response was measured using the Dynamic Retinal Vessel Analyzer. FMD was determined using a high resolution ultrasound system, measuring brachial artery diameter reactivity during reperfusion after arterial occlusion.

Results The flicker response of both retinal arteries and veins was significantly reduced in the two patients groups. Likewise, FMD was significantly reduced in patients as compared to healthy controls. However, only a weak correlation between flicker induced vasodilatation and FMD was observed.

Conclusion The study confirms evidence that flicker responses and FMD is reduced in the selected patients groups. Whether the weak correlation between FMD and flicker is due to the different stimulation type, the different vascular beds measured or other mechanisms has yet to be investigated.