bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcomes after proton beam therapy for large choroidal melanomas in 492 patients
Authors: Bensoussan E. , Baillif S. , Maschi C. , Caujolle J.P. , Thariat J.
Published: September 2016

Purpose

To evaluate proton beam therapy (PBT) as a mean to preserve the eye and spare some vision while not deteriorating survival in patients with large choroidal melanomas.

Methods

This is a retrospective, consecutive cohort study of patients with T3‐4 choroidal melanomas according to the 7th edition of the American Joint Cancer Classification treated with PBT over a 24‐year period.

Results

492 patients were included. Mean tumor thickness and diameter were 8.77 (2–15) mm and 14.91(7–24.1) mm, respectively. Mean macular and optic disc distance were 4.56 (0–19.9) mm and 4.59 (0–22.1) mm, respectively. Mean follow‐up was 61.9 months. Rates of neovascular glaucoma (NVG) and enucleation (mainly for local recurrence or NVG) were 27.0 and 19.5%, respectively. Enucleation rates decreased over time. The five‐year local control was 94%. Mean baseline visual acuity was 20/63, and visual acuity ≥20/200 was preserved in 20% of patients. At five years, 25% of T3 patients presented with metastasis, overall and specific survival rates were 65 and 75%, respectively.

Conclusions

Local control after PBT remained good with increasingly manageable complications and fewer secondary enucleations over time for these large melanomas. As PBT does not seem to deteriorate survival in these patients having a high risk of metastasis, PBT may be considered as a safe and efficient alternative to enucleation in patients with large choroidal melanoma, and may help to spare some vision.
Longitudinal changes in retinal nerve fiber layer thickness in a healthy caucasian population
Authors: Popa Cherecheanu A. , Barac C. , Miu J. , Roncea T. , Nicolae A. , Duta S. , Pirvulescu R.
Published: September 2016

Purpose

To study the loss of retinal nerve fiber layer thickness over time in healthy subjects.

Methods

In this prospective longitudinal study 65 female and male subjects (age 62.7 ± 10.6 years) were included. In the present study an optic disc cube scan protocol was employed to measure RNFLT using the Cirrus HD‐OCT. The OCT scans were repeated in intervals between 3 and 6 months, the number of OCT scans was between 3 and 11 and the average observation period was 30 months. Linear mixed models were used to fit OCT data.

Results

On average a loss of RNFLT was seen during the average observation period. In a multiple regression model two factors influenced the results: age and baseline RNFLT. The greater the RNFLT value at baseline the stronger the loss of RNFLT. When dividing the subjects into 2 age groups a decrease in RNFLT was only seen in older subjects (70.2 ± 6.1 years), but not in younger subjects (55.1 ± 8.6 years). This decrease of average RNFLT in the older age group was −0.61 μm/year (95% confidence interval −1.10 μm/year to −0.11 μm/year).

Conclusions

The present study indicates a loss of RNFLT thickness over time in healthy subjects. This decrease was seen in older subjects, but not in younger individuals. The age‐dependent loss of RNFLT should be considered when progression is analyzed in patients with neurodegenerative diseases such as glaucoma, multiple sclerosis or Alzheimer's disease.
Contribution of dual fluorescein and indocyanine green angiography to the appraisal of posterior involvement in birdshot retinochoroiditis and Vogt‐Koyanagi‐Harada disease
Authors: Balci Ö. , Jeannin B. , Herbort C.P.
Published: September 2016

Purpose

To assess the levels of retinal versus choroid involvement in two stromal choroiditis entities, birdshot retinochoroiditis (BRC) and Vogt‐Koyanagi‐Harada (VKH) disease in initial onset non treated disease.

Methods

This retrospective study included patients diagnosed with BRC and VKH, seen during initial onset disease at the Centre for Ophthalmic Specialized Care, Lausanne, Switzerland. Angiographic signs were quantified, using an established dual FA and ICGA scoring system for uveitis, and the FA/ICGA ratios were compared between diseases.

Results

Among 1,739 patients with uveitis seen from 1995 to 2014, 7 newly diagnosed BRC patients and 4 patients with newly diagnosed VKH disease were included in the study. Patients with BRC and VKH had mean FA angiographic scores of 16.64 ± 3.75 and 4.25 ± 1.83; mean ICGA angiographic scores of 21.00 ± 3.48 and 25.25 ± 3.84; and mean FA/ICGA ratios of 0.79 ± 0.21 and 0.17 ± 0.09, respectively.

Conclusions

This study showed the differential involvements of the retina and choroid in BRC and VKH. Choroid was predominantly involved in both diseases, which clearly indicated that ICGA was the method of choice, and that it should be performed in conjunction with FA. Also, the FA/ICGA ratio highlighted the fundamental differences between BRC and VKH. VKH had a purely choroidal origin of inflammation, and BRC had both retinal and choroidal origins of inflammation.
Molecular mechanisms of X‐linked retinitis pigmentosa
Authors: Zhang X. , Shu X.
Published: September 2016

Purpose

Retinitis Pigmentosa is a class of inherited retinal degeneration that causes progressive vision impairment even blindness. The mutations of Retinitis Pigmentosa GTPase Regulator (RPGR) gene account for up to 20% of RP cases. RPGR protein is highly expressed at the connecting cilium of vertebrates’ photoreceptors. RPGR protein has the function of regulating protein trafficking from basal body to axoneme. The trafficking is controlled by the protein complex formed by RPGR, RPGRIP1 and IFT proteins, although its precise function yet to be identified. RPGR−/− mice model was employed for investigating disease mechanisms during retinal degeneration.

Methods

Cell death pathway and protein trafficking were detected by immunohistochemistry.

Results

The retina of RPGR−/− mice started to undergo degeneration from 3M old. The caspase dependent cell death pathway was found to be activated during degeneration. The Apoptosis Inducing Factor existed in outer nuclear layer indicated that caspase‐independent apoptosis also contributed to cell death. The activated microglia, showed migration from outer plexiform layer to ONL in the retina of RPGR−/− mice and the downstream inflammation pathway were activated in RPGR−/− retina. Prior to the onset of retinal degeneration, the key elements involved in the phototransduction such as rhodopsin already mislocalized and accumulated in inner segment and outer nuclear layer. The mislocalization may result from the abnormal formation of the regulator of membrane trafficking Rab8 in RPGR−/− mice that controls the fusion of rhodopsin transport carrier and directs the cargo delivery across the CC.

Conclusions

In Conclusion, multi‐pathways were involved in the photoreceptor cell death and the deficiency of RPGR led to abnormal localization of the crucial proteins that participate in photoreceptor maintenance and phototransduction.
Involvement of abnormally‐activated CD44+ cells migrating from the iris to the center of the cornea in Fuchs Endothelial Corneal Dystrophy
Authors: He Z. , Thuret G. , Jun A.S. , Muraine M. , Kallay L. , Toubeau D. , Pereira S. , Bergandi F. , Gain P.
Published: September 2016

Purpose

Normal regeneration of the adult corneal endothelium and cellular mechanisms involved in Fuchs endothelial corneal dystrophy (FECD) remain poorly understood. Aim: to present original observations establishing common ground between both mechanisms in order to open new perspectives in their understanding.

Methods

30 corneal buttons of FECD, and of other corneal diseases, 40 healthy whole corneas, and 6 whole corneas with early stages of FECD were used. Mean donor age was 72 years. Immunostaining on flat mounted corneas highlighted the expression of corneal endothelial cell (CEC), of stem cell, and of extracellular matrix (ECM) markers.

Results

The central endothelium of FECD and the extreme peripheral endothelium of healthy corneas shared common features: a weak expression of CEC markers (Na+/K+ ATPase, ZO‐1, COX IV, NCAM, CD166), expression of stem cells markers (nestin, c‐myc, telomerase, CD44), similar characteristics in Descemet membrane (Guttae and Hassal‐Henle bodies, high expression in col I, IV and V). An anatomical continuity and cell migration from the iris root, through TM, until the extreme peripheral endothelium was highlighted using col I and CD44. Similar CD44+ cells, and pseudo guttae were also observed in the central endothelium of corneal buttons with irido‐corneal synechiae.

Conclusions

Results suggest that a population of iris‐derived CD44+ cells migrate through the TM to the extreme periphery to constitute a source for endothelium regeneration in healthy corneas; their abnormally‐activated migration toward the center might cause FECD.
Could 24‐S‐hydroxycholesterol play a role in Müller glial cell's membrane dynamics in the rat
Authors: Bron A. , Ferrero A. , Gambert‐Nicot S. , Brétillon L. , Acar N. , Creuzot‐Garcher C.
Published: September 2016

Purpose

The catabolism of cholesterol in neurons leads to a more hydrophilic compound soluble form, the 24‐S‐hydroxycholesterol by means of an enzyme the CYP46A1.The aim of this study was to analyse the implication of 24‐S‐hydroxycholesterol (24‐S‐OHC) on Müller glial cells (MGC) membrane dynamics in the rat.

Methods

MGC were grown in vitro from retinas of 10‐day‐old Long Evans rats. Cells were treated with 24‐S‐OHC (treatment) or ethanol (control) for 2 min or 6 h. From twenty millions of MGC in each group, lipid‐rafts were obtained after a 1% Lubrol lysis and an ultra centrifugation (180,000 g – 20 h – 4°C). The following proteins: caveolin, flottilin, connexin 30 and 43, CRALBP, DHAPAT, GFAP and vimentin were analysed using Western blotting on all fractions (lipid‐rafts and non‐rafts). MGC membrane fluidity was studied in vitro with two different techniques: anisotropy measurements performed with the lipophilic fluorescent probe TMA‐DPH and fluorescence recovery after photobleaching (FRAP) observed using confocal microscopy.

Results

24‐S‐OHC treatment on in vitro MGC increased the expression of GFAP and delocalized GFAP in the lipid‐raft fraction; 24‐S‐OHC treatment induced a delocalization of DHAPAT protein out of the lipid‐rafts fraction. Anisotropy was decreased with the 24‐S‐OHC treatment (difference: 5.1 × 10−3; p < 0.01) revealing an increase of the membrane fluidity. This increase was confirmed by the FRAP technique, which showed a shorter time of fluorescence recovery for the treated cells.

Conclusions

This study showed that 24‐S‐OHC could be a candidate leading a key role in the activation of MGC, disturbing lipid‐raft organization by changing the localization of signalization proteins and increasing membrane's fluidity.
Essentials of a good article
Authors: Stefansson E.
Published: September 2016

The intrinsic quality of a scientific article depends first and foremost on its scientific content. However, the way in which the scientific material is presented and the paper is written may determine whether the scientific content will ever receive the attention it deserves. There may not be any perfect recipe for a perfect paper, but it is possible to point out some general characteristics of good papers, and we will try to do so. Our guidance is based on convention and personal preference, reflecting our experience as authors, reviewers and editors. We hope our advice will be useful, especially to those who are starting to write scientific papers.
Wave‐amplitude differences between corneal and conjunctival electrodes for multifocal electroretinogram
Authors: Munoz‐Negrete F.J. , Rebolleda G. , Garcia Garcia A.
Published: September 2016

Purpose

To compare the wave amplitude of multifocal electroretinogram (mfERG) responses from DTL electrode located on the conjunctival fornix (fDTL) and ERG‐jet contact lens electrode (CL).

Methods

Thirty patients and 18 matched healthy volunteers were evaluated. Wave amplitude and level of discomfort with each electrode were compared in both patients and healthy volunteers. Comparisons among wave amplitudes were performed using Intraclass Correlation Coefficient

Results

mfERG by corneal electrode provided the highest wave amplitude in both healthy subjects and patients (p < 0.005), but it associated the highest discomfort (p < 0.001) and the highest rate of dislocations. CL was able to differentiate patients from controls just in the ring 1 (central 2°) of the mfERG. By contrast, fDTL provided the lowest wave amplitude but better discriminated between patients and control group in ring 1 (central 2°) and 2 (2–5°) of the multifocal ERG. cDTL produced significant more artifacts in both groups (p < 0.001).

Conclusions

Although mfERG wave amplitude measurements were correlated, they cannot be directly compared, so it is mandatory to create an appropriate normative database with each electrode. Despite providing the lowest amplitudes, fDTL seems to offer the best features to perform mfERG regarding discomfort, number of artifacts and diagnostic capability.
Treatment of visual impairment in patients with Leber's Hereditary Optic Neuropathy (LHON) using Idebenone (Raxone®)
Authors: Metz G. , Hasham S. , Catarino C. , Klopstock T.
Published: September 2016

Purpose

LHON is an orphan mitochondrial disorder affecting the retinal ganglion cells leading to permanent blindness from which recovery is rare. More than 90% of patients harbor one of three mitochondrial DNA mutations in the genes coding of complex I of the respiratory chain. Idebenone, a short‐chain benzoquinone, is a potent antioxidant and also interacts with the electron transport chain facilitating mitochondrial electron flux. Due to these properties idebenone (Raxone®) has been investigated for the treatment of LHON and we summarize the evidence available for efficacy based on a placebo controlled trial and from clinical practice.

Methods

Visual acuity data from a randomized study (RHODOS), from case reports, retrospective cohort studies, an Expanded Access Program (EAP) and a natural history case report survey have been collected in a database of approximately 500 patients. The disease progression based on natural history data and from the Placebo treated patients are compared to the outcome for patients treated with idebenone with respect to the prevention of vision loss and the recovery of lost vision.

Results

In RHODOS, the number of patients experiencing a clinically relevant recovery after 6 months of treatment was 10.3% in the Placebo group and 30.2% in the idebenone treated group. Patients in the EAP showed a recovery rate of 30.6% after 6 months of treatment increasing to 49.3% when comparing the final outcome after 15 m (mean treatment) to the VA at nadir. The number of patients experiencing vision loss to above 1.0 logMAR VA was lower in RHODOS and in the EAP when compared to the datasets of untreated patients.

Conclusions

A large body of evidence demonstrates that patients with LHON benefit from Raxone treatment and that the drug is well tolerated.
BAP1 germline mutations in uveal melanoma patients without family history of eye cancer
Authors: Turunen J. , Markkinen S. , Wilska R. , Raivio V. , Täll M. , Lehesjoki A.E. , Kivelä T.
Published: September 2016

Purpose

Germline pathogenic variants of the BRCA‐1 associated protein‐1 (BAP1) gene predispose to uveal melanoma and several other cancers. Testing for germline BAP1 mutations should be performed if typical BAP1 cancer predisposition syndrome tumors have been diagnosed in the family. We report the frequency of germline pathogenic variants of BAP1 in consecutive Finnish uveal melanoma patients without known history of eye cancer.

Methods

In Finland, uveal melanomas are treated centrally in the Ocular Oncology Service, Helsinki University Hospital. We collected clinical data and genomic DNA from 239 of 389 consecutive patients diagnosed from January 2010 to December 2015. Patients with verified family history of eye cancer were excluded. Fifteen patients had died before the study started and could not be sampled. The exons and exon‐intron junctions of BAP1 were sequenced.

Results

We found only one probable pathogenic germline variant, a donor splice site mutation in a highly conserved region immediately after exon 2 in a 57‐year‐old male patient. Three of his family members had been diagnosed with typical BAP1‐related cancers (cutaneous melanoma, mesothelioma, and renal cell carcinoma). The mutation was not found in 61,486 controls from the ExAC (http://exac.broadinstitute.org). The frequency of germline BAP1 mutation in patients without any family history of eye cancer was 0.4% (1/239, 95% CI 0.01 to 2.2).

Conclusions

The frequency of BAP1 germline pathogenic variants in the Finnish patients with uveal melanoma without family history of ocular cancer is low. The family history of typical BAP1‐related cancers was informative, and should routinely be obtained to guide the BAP1 genetic testing.
Diagnosis and management of cytomegalovirus anterior uveitis/endothelitis in immunocompetent patients in 2 European referral centers
Authors: Antoun J. , Caspers L. , Groot‐Mijnes J. , Motulsky E. , Dam‐van Loon N.H.T. , Makhoul D. , Willermain F. , Judice Relvas L.
Published: September 2016

Purpose

To evaluate the methods leading to the diagnosis of CMV anterior uveitis (AU) and/or endotheliitis from 2 uveitis tertiary referrals centers and to assess the outcome after topical ganciclovir treatment.

Methods

Retrospective study of patients with a clinical and biological diagnosis of CMV AU/endothelitis demonstrated by a positive polymerase chain reaction (PCR) and/or Goldmann‐Witmer coefficient (GWc). The Belgian patients were treated with topical ganciclovir once the biological diagnosis was confirmed. The number of recurrences was evaluated in the pre‐ and post‐treatment period.

Results

We report a series of 21 patients (15 from Brussels and 6 from Utrecht) presenting clinical characteristics of CMV AU and/or endothelitis with a positive PCR and/or GWc for CMV. PCR was positive in 15/21 (71.4%) patients, while GWc was positive in 8/9 (88.9%), including 6 patients initially tested for PCR and GWc and 3 secondary tested for GWc when the PCR was negative. 2/9 patients (22.2%) were GWc+/PCR+, 6/9 patients (66.7%) GWc+/PCR‐ and 1/9 patient was GWc‐/PCR+ (11.1%). Aqueous tap was repeated in 9 of the 15 Belgian patients (60%) (2 times in 6 cases, 3 times in 3 cases) to get the biological confirmation of CMV AU/endothelitis. Mean follow up duration was respectively 19.2 ± 23.8 and 46.7 ± 29.7 months in the pre‐ and post‐treatment period. Patients had a significantly lower number of recurrences/year post‐treatment (0.76 ± 0.57) than in the pre‐treatment period (3.76 ± 2.44) (p = 0.001).

Conclusions

Repeated aqueous taps in order to perform PCR and GWc were found to be helpful to confirm biologically the clinical diagnosis of CMV AU/ endothelitis. Our results also suggest that patients with topical ganciclovir have a decreased frequency of CMV‐AU/endotheliitis recurrence and keep a relatively good vision over time.
The αA‐crystallin gene expression in differentiating lens fiber cells, FGF signaling, and transcriptional factories
Authors: Cvekl A. , Limi S. , Zhao Y. , McGreal R. , Xie Q. , Zheng D.
Published: September 2016

Purpose

Embryonic lens development requires intricate temporal and spatial control of gene expression that is executed through specific gene regulatory networks regulated by FGF signaling. The αA‐crystallin is the most abundant mammalian lens protein; transcriptional studies of this gene provide detailed insights into the molecular mechanisms governing lens fiber cell differentiation.

Methods

Dynamic changes in chromatin structure and gene expression during lens developments were evaluated by a combination of RNA‐seq and ATAC‐seq. Expression of αA‐crystallin (ch1) and other crystallins (Cryga, Crybb1, and Crybb3, localized on chromosomes 1 and 5, respectively) in individual nuclei of the developing mouse lens were analyzed by RNA‐FISH. Transgenic mice with c‐Maf promoter were generated and expression of EGFP was evaluated in mouse embryos. Localization of c‐Jun, c‐Maf, Etv5/ERM, and Pax6 was determined by ChIP using the c‐Maf and Cryaa loci and mouse lens chromatin. Co‐transfection experiments with c‐Jun and Etv5 were conducted using c‐Maf and αA‐crystallin reporters.

Results

Transcriptional factories, a subset of topologically associating domains (TADs), are formed between different crystallin loci in lens cell nuclei. These specific TADs are enriched by RNA polymerase II and other proteins. Novel FGF2‐responsive region in the c‐Maf promoter was found. Both c‐Maf and Cryaa regulatory regions contain arrays of AP‐1 and Ets‐binding sites determined by ChIP assays.

Conclusions

Collectively, these studies show that the lens fiber cell nuclei spatially organize crystallin loci into TADs, and that FGF signaling up‐regulates expression of αA‐crystallin both directly and indirectly via up‐regulation of c‐Maf. These molecular mechanisms are applicable for other crystallins and genes highly expressed in terminally differentiating lens fibers.
Clinical and radiological evidence of meningioma growth due to gestational or exogenous hormones: 2 cases
Authors: Marcelis W. , Sys C. , Acou M. , Leroy B.P. , Kestelyn P. , De Schryver I.
Published: September 2016

Purpose

We report 2 cases with documented hormonal growth of meningiomas, one probably caused by exogenous hormonal therapy, one by pregnancy‐related hormonal changes.

Methods

Observational report about 2 cases with either reproductive or exogenous hormonal growth of meningioma. Both patients underwent a full ophthalmological work up, including MRI‐volumetry.

Results

A 42 year‐old man presented with unilateral blindness. Examination showed no light perception in the left eye. MRI of the brain revealed 11 meningiomas, with a large one compressing the optic nerve of the left eye. He had been treated for 23 years with cyproterone acetate (CPA) 100 mg/day to reduce his undesirable sexual behavior. CPA treatment was stopped immediately, resulting in a decrease of volume of the large meningioma of 250 cc.

A 33 year‐old woman was referred because of blurred vision, migraine with hemiparesis and aphasia following a twin pregnancy. The left eye showed papillary oedema. The right eye was blind due to an unknown cause at the age of 7. MRI at that time was negative. She had just delivered twins after a 3rd pregnancy over only 2 years. MRI showed large meningiomas in the left optic canal. Since they were inoperable, a shunt to release intracranial pressure was placed. The papillary edema resolved and the volume of the meningiomas decreased.

Conclusions

Two unrelated cases of hormone‐induced growth of meningiomas are described. Hormone withdrawal results in a decrease of meningioma volumes. These findings illustrate the role of female sex hormones in the development and growth of meningiomas.
Normal values for fundus perimetry with the MAIA microperimeter and short‐term repeatability evaluation
Authors: Baudin F. , Assad G. , Meillon C. , Koehrer P. , Bron A. , Creuzot C.
Published: September 2016

Purpose

To assess retinal sensitivity by means of microperimetry and to evaluate the intersession fluctuation using the MAIA microperimeter in healthy volunteers.

Methods

Prospective, monocentre study. Fifty‐six healthy volunteers (age range, 20–80 years), underwent an automatic, full‐threshold microperimetry of the central field (custom grid, area of 10° in diameter, 37 stimulated points), with the MAIA microperimeter (CenterVue, Padova, Italy). A subgroup of 24 subjects was retested after 1 h (test 2) and 1 week (test 3) to determine the repeatability of the technique. A subgroup of 22 subjects was also tested on the OPKO microperimeter (Optos, Dunfermline, Scotland) (area of 10° in diameter, 28 stimulated points).

Results

Median age was 30 years [25.3–47.8]. The overall mean sensitivity for test 1 was 29.4 ± 1.4 dB, 29.8 ± 1.0 dB for test 2 and 29.9 ± 1.1 dB for test 3, respectively. Linear regression analysis showed a significant 0.5 dB sensitivity loss for each decade of life (r² = 0.27). In a subset of 24 subjects, the repeatability of the test performed at 3 separate visits showed a statistically significant difference between test 1 and 3 (p < 0.004). Test 2 and 3 showed consistent values over time (p = 0.160). Furthermore, the MAIA showed higher threshold values than the OPKO for all test locations. Linear regression of the perimetric results showed significant correlation between the 2 machines (r = 0.44; p < 0.001).

Conclusions

This study found an age‐related macular sensitivity loss. These findings are in agreement with previous data obtained with the MP1 and the OPKO microperimeters. The increase in sensitivity between test 1 and test 2 and 3 should be taken into account in clinical practice. Automatic fundus perimetry with the MAIA microperimeter allows for accurate, repeatable examination, if a training session is performed.
Licence to save – a UK survey of anti‐VEGF use for the eye in 2015
Authors: Shalaby A. , Lockwood A. , Bush A. , Lewis K. , Di Simplicio S. , Meredith P.
Published: September 2016

Purpose

The difference in cost of Anti‐vascular endothelial growth factor (anti‐VEGF) injections is significant. Prices, according to the British National Formulary (BNF), are: ranibizumab; £742 per single injection vial, aflibercept; £816 per single injection vial, and bevacizumab £242.66, but in standard practice each vial is divided into 20 injections, giving a price of £12.13 per injection. Because patients require repeated injections these costs are multiplied many times over.

We hypothesised the majority of injections would be with the less expensive drug, bevacizumab. We therefore performed a survey of all United Kingdom (UK) NHS ophthalmological units.

Methods

A freedom of information (FOI) request was submitted to all UK NHS Trusts and Health Boards requesting the number and cost of intravitreal injections of ranibizumab, aflibercept, and bevacizumab prescribed during the month of January 2015. Non‐NHS units were excluded.

Costs per month were determined by multiplying injection numbers with BNF (British National Formulary) prices and then by 12 for yearly costs.

Results

A total of 189 FOI requests were sent. The overall response rate was 95.8%.

Ranibizumab was used 30,634 times (61%), Aflibercept 18,095 (36%) and Avastin was only 1410 (3%).

Costs per month were: £27,276,514 for Ranibizumab, £17,683,373 for Aflibercept, £20,530 for Bevacizumab.

Total monthly costs were: £44,980,416.00. Estimated annual costs were: £539,764,992.00.

Conclusions

These results show the anti‐VEGF injection cost to the NHS. Contrary to hypothesis the vast majority (97%) were still with the more expensive drugs ranibizumab and aflibercept. If all injections used divided bevacizumab, the estimated drug cost would be £607,749 (£729,500 incl. VAT) saving the NHS £449,196,354 (£539,035,492 incl. VAT) per year. With 5% remaining unaccounted for the savings may be greater.
Visual dysfunction and its correlation with retinal changes in patients with Parkinson disease
Authors: Vilades E. , Garcia‐Martin E. , Satue M. , Rodrigo M.J. , Obis J. , Cipres Alastuey M.
Published: September 2016

Purpose

To evaluate visual dysfunction and its correlation with structural changes in the retina in patients with Parkinson disease (PD).

Methods

Patients with PD (n = 37) and controls (n = 37) underwent visual acuity (VA), color vision (using the Farnsworth and L'Anthony desaturated D15 color tests), and contrast sensitivity vision (CSV; using the Pelli Robson chart and CSV 1000E test) evaluation to measure visual dysfunction. Structural measurements of the retinal nerve fiber layer (RNFL), and macular and ganglion cell layer (GCL) thicknesses were obtained using spectral domain optical coherence tomography (SD‐OCT). Comparison of obtained data and correlation analysis between functional and structural results were performed.

Results

VA (in all different contrast levels) and all CSV spatial frequencies were significantly worse in PD patients than in controls (p < 0.05). Color vision was significantly affected (p < 0.05) based on the L'Anthony color test. Macular thinning was detected in the central, outer (inferior and temporal), and superior (inner and outer) sectors (p < 0.05), and the RNFL had significant thinning in the temporal quadrant (p < 0.05). Significant GCL loss was observed in the superior and superonasal sectors and the minimum GCL + inner plexiform layer (p < 0.05). CSV was the functional parameter most strongly correlated with structural measurements in PD. Color vision was associated with most GCL measurements. Macular thickness was strongly correlated with macular volume and functional parameters (r > 0.70, p < 0.05).

Conclusions

Patients with PD had visual dysfunction that correlated with structural changes evaluated by SD‐OCT. Macular and GCL measurements may be reliable indicators of visual impairment in PD patients.
Changes in choroidal thickness after ranibizumab and aflibercept Therapy for treatment‐naïve wet age‐related macular degeneration
Authors: Kang H.G. , Kim J.S. , Lee J.H. , Kim Y.I. , Lee S.H.
Published: September 2016

Purpose

To compare the changes in subfoveal choroidal thickness between ranibizumab and aflibercept therapy for treatment‐naive wet age‐ related macular degeneration.

Methods

This retrospective, observational study included 47 eyes of treatment‐naive wet age‐related macular degeneration patients who were followed up for at least 6 months after initial injection. All eyes were treated with 3 consecutive monthly injection of ranibizumab or aflibercpt, and treated with PRN injection of anti‐vascular endothelial growth factor after 3 consecutive monthly injection. Subfoval choroidal thickness was measured using enhanced depth imaging optical chorence tomography.

Results

In the ranibizumab injected group (25 eyes), mean changes in choroidal thickness was −9.80, −16.86, −25.08, −10.40 μm at 1, 2, 3, 6 months after initial injection respectively. In the aflibercept injection group (22 eyes), mean changes in choroidal thickness was −24.30, −32.73, −37. 52, −15.77 μm at 1, 2, 3, 6 months after initial injection respectively. The mean changes in subfoveal choroidal thickness was significantly greater in the aflibercept injected group (p < 0.05) at 1 month, but there was no significant difference between two group at 2, 3, and 6 months after initial injection (p > 0.05).

Conclusions

Subfoveal choroidal thickness was decreased after ranibizumab and aflibercept therapy. The mean changes in subfoveal choroidal thickenss was greater in aflibercept injected group at 1 month, but there was no significant difference between two therapy at 2, 3, and 6 months after initial injection.
Clinical features of cataract extraction with negative power intraocular lens implantation in high myopia patients
Authors: Choi J.B. , Shin W.B. , Kim M.K.
Published: September 2016

Purpose

To evaluate the clinical features of high myopic eyes with cataracts implanted with negative power intraocular lenses (IOLs) at the time of cataract surgery.

Methods

A retrospective chart review was conducted of 18 eyes of 14 patients who underwent cataract surgery with negative power IOLs and 10 eyes in 9 patients with low power IOLs. We investigated axial length, IOL power, preoperative and postoperative best‐corrected visual acuity (BCVA) and preoperative and postoperative spherical equivalent (SE) refractive errors.

Results

Mean BCVA showed significant improvement in both groups. We measured postoperative SE refraction and the difference between the mean intended and the mean achieved SE refractive errors in the negative power group (17 eyes) was +1.59 ± 1.34 D and +0.31 ± 0.50 D in the low power group.

Conclusions

BCVA was significantly improved in the majority of eyes, although they had myopic macular degeneration or posterior staphyloma. However, the mean achieved postoperative SE refraction was more hyperopic than the predicted postoperative SE error. Additionally, hyperopic refractive error was greater in the negative power group than the low power group. Therefore, we recommend that postoperative hyperopic refractive error should be considered when performing cataract surgery in high myopic patients.
Validation of the STARS risk assessment tool for age‐related macular degeneration in an Algerian population
Authors: Delcourt C. , Lazreg S. , Sanchez A. , Bandello F. , Nouri M.T.
Published: September 2016

Purpose

A risk assessment tool for age‐related macular degeneration (AMD) has been previously developed and validated in two European countries (Italy, France). The objective of the present study was to validate its use in an Algerian population.

Methods

The STARS (Simplified Théa AMD Risk‐assessment Scale) questionnaire is a simple 13‐item, self‐administered questionnaire, including questions on socio‐demographic characteristics, family history of AMD, systemic and ocular risk factors. We included 1,183 patients over 55 years of age from 23 Algerian ophthalmologists. Patients completed the questionnaire, and ophthalmologists performed a fundus examination for AMD diagnosis (early AMD if soft drusen and/or pigmentary abnormalities; late AMD if atrophic and/or neovascular AMD). The validity of the final score was determined using ROC curves and Hosmer and Lemeshow testing. Patients were classified as low (score 0–9), moderate (10–19) or high risk (scores of 20+).

Results

Complete data was obtained for 942 (79.6%) patients, among whom 53 (5.6%) had late AMD and 288 (24.1%) had early AMD. The area under the ROC curve was 0.80, indicating good discrimination. The Hosmer and Lemeshow test was not statistically significant (p = 0.60), showing a good adaptation of the model to the data. Only 26 of the 662 (3.9%) patients without AMD were categorized as high risk and only 8 of the 53 patients (15%) with late AMD were categorized as low risk.

Conclusions

This study confirmed the validity of this short risk assessment tool, which shows good discrimination and high feasibility also in a North‐African country. Early diagnosis of AMD is key to improve disease outcomes in patients. STARS is a promising questionnaire that allows early, simple and fast identification of patients at risk of AMD.
UM Cure 2020 – A consortium of European experts in uveal melanoma to identify new therapies for patients with metastatic disease
Authors: Coupland S. , Kalirai H. , Jager M. , Jochemsen A.G. , van der Velden P.A. , Snaar‐Jagalska B.E. , Dhomen N. , Marais R. , Romanowska Dixon B. , Elas M. , Mione M.C. , Valente A. , Ryll B. , Ruijtenbeek R. , Prestat A. , Hafsi H. , Barnhill R. , Cassoux N. , Decaudin D. , Lantz O. , Piperno‐Neumann S. , Stern M.H. , Roman‐Roman S.
Published: September 2016

Purpose

Uveal melanoma (UM) is a rare intraocular tumour with an incidence of 5 cases per million individuals per year. Up to 30% of UM patients develop metastases, most often in the liver, and there is no therapy to either prevent or treat these metastases. Despite new discoveries in the genetic and molecular background of the primary tumour, little is known about the metastatic disease.

In UM Cure 2020, funded by European Union's Horizon 2020 programme, we will identify and validate at the preclinical level novel therapeutic approaches for the treatment of UM metastases (www.umcure2020.org). The Consortium brings together major EU experts in clinical, translational and basic research on UM, as well as patient representatives and innovative biotech companies.

Methods

An ambitious multidisciplinary approach is proposed to move from patient tissue characterisation to preclinical evaluation of single or combinations of drugs. We will characterise the genetic landscape of metastatic UM and its microenvironment, perform proteomic studies to address signalling pathway deregulation and establish novel relevant in vitro and in vivo UM models. Underpinning this will be our virtual sample registry, linking existing biobanks into a harmonised network, which will prospectively collect primary and metastatic UM samples.

Results

In parallel, we are already evaluating in the first phase of the project the efficacy of a series of active compounds using partners’ available models. In addition to the initiation of UM‐dedicated clinical trials, dissemination of results includes initiatives to increase patient information and disease awareness, in particular by supporting the formation of a European UM patient network.

Conclusions

The UM Cure 2020 Consortium holds great potential to make significant advances in the treatment of metastatic UM, at present an incurable disease.
Spectral domain optical coherence tomography for detecting retinal arterial macroaneurysm
Authors: Ascaso F.J. , Berniolles J. , Bartolomé I. , Martínez M. , Esteban O. , Sánchez I. , Almenara C. , Del Buey M.A.
Published: September 2016

Purpose

Retinal arterial macroaneurysm (RAM) is an acquired sacular dilatation of a retinal arterial vessel. It is commonly associated with systemic arterial hypertension, vascular disease and women. It often appears in the sixth decade of life or older. RAMs are usually classified into three forms: quiescent, hemorrhagic and exudative. The first of them are asymptomatic, the exudative form courses with loss of visual acuity and the hemorrhagic form is responsible of hemathomas (either subretinal, intraretinal, retrohyaloid or intravitreal). The aim of this study was to describe retinal structural changes and tomographic features associated with RAM.

Methods

A case report of an otherwise healthy middle aged man who was diagnosed with a RAM in his right eye and who underwent Heidelberg spectral‐domain optical coherence tomography (SD‐OCT).

Results

SD‐OCT was able to demonstrate and measure the RAM and the upstream/downstream vessel. Likewise, it showed other related OCT changes in the adjacent retina such as the presence of subretinal fluid and macular edema.

Conclusions

SD‐OCT is an effective tool for detecting retinal macroaneurysms. It also provides important supplementary clinical information that may be helpful in planning the management of macroaneurysm, without the need for ancillary tests.
A new electroretinogram function that can move the centre of the multifocal hexagonal stimulus array
Authors: Suzuki N. , Yamane K.
Published: September 2016

Purpose

We can examine declines in visual sensitivity at arbitrary points on the retina using a precise perimetry device with a fundus camera function. However, the retinal layer causing the decline in visual sensitivity can not be identified. To investigate cryptogenic diseases, such as macular dystrophy, acute zonal occult outer retinopathy and multiple evanescent white dot syndrome, we studied a new electroretinogram function that can move the centre of the multifocal hexagonal stimulus array.

Methods

An electroretinographic optical system, specifically perimetric optical system, was added to an experimental device with the same optical system as a fundus camera. We also added an Edmund infrared camera EO‐0413, a lens with a focal length of 25 mm, a 45‐degree cold mirror, a halogen lamp and an 8‐inch monitor. Software was generated to show the multifocal hexagonal stimulus array on the monitor using C++Builder XE8 and to move the centre of the array up and down as well as back and forth. We used National Instruments’ USB‐6008 and their system design platform LabVIEW 2015 for data retrieval. The Nihon Kohden plate electrode NE‐113As were used to measure electrodermal activities around the eyes. Some contact lens electrodes were used to measure electrical potentials of retina.

Results

We used a multifocal hexagonal stimulus array with 37 elements in the software. The centre of the multifocal hexagonal stimulus array could be adjusted to the same position as the examination target of the precise perimetry.

Conclusions

We successfully added this new electroretinogram function to the experimental ophthalmologic device.
Unilateral carcinoma‐associated retinopathy: diagnosis, serology and treatment
Authors: Roels D. , Ueno S. , Kondo M. , Leroy B.P.
Published: September 2016

Purpose

To report a case of unilateral CAR with clinical and ERG normalization after radical hysterectomy combined with steroids and Rituximab.

Methods

Work‐up included extensive clinical and electrophysiological testing. Also, serological work‐up for antiretinal antibodies and oncological screening was organized.

Results

A 45‐year‐old female presented with progressive unilateral photopsias, photophobia and relative central scotoma in the RE since 6 weeks prior. BCVA was 1.0 in BE. Biomicroscopy, IOP and fundus exam were unremarkable. Also, colour vision, AFI, OCT and EOG were normal. VFs showed decreased central sensitivity in the RE. ERG showed an electronegative combined and ON‐bipolar response. A diagnosis of CAR was suspected. Radical hysterectomy was performed after a diagnosis of an undifferentiated cystic adenocarcinoma of the right ovary, followed by adjuvant chemotherapy. A whole body PET scan revealed no metastasis. Treatment with rituximab monoclonal antibodies in combination with corticosteroids was initiated. The patient tested positive for serum auto‐antibodies against TRPM1, a transient receptor potential cation channel expressed in ON‐bipolar cells. After treatment there was progressive improvement in symptoms and the ERG normalised. Serology confirmed complete clearance of auto‐antibodies.

Conclusions

Although extremely rare, unilateral CAR does occur and in cases with high clinical suspicion an oncological work‐up is mandatory. Aggressive treatment combining surgery, steroids and Rituximab can lead to clinical and ERG normalization with clearing of antiretinal antibodies.
Changes of central macular thickness and retinal nerve fiber layer thickness in eyes with Vogt‐Koyanagi‐Harada disease: a 2‐year follow‐up study
Authors: Shin K.S. , Han Y.S. , Kim M.S. , Kim J.Y.
Published: September 2016

Purpose

To prospectively investigate the change in central macular thickness (CMT) and retinal nerve fiber layer (RNFL) thickness in eyes with Vogt‐Koyanagi‐Harada (VKH) disease in through 24 months follow‐up.

Methods

Twelve eyes of 6 treatment‐naïve patients with acute VKH disease associated with optic disc swelling and serous retinal detachment and 30 eyes of 15 normal individuals were enrolled to investigate the changes of CMT and average RNFL thickness. Retinal thickness were measured at first visit and months 6, 12 and 24 via spectral domain optical coherence tomography (SD‐OCT).

Results

CMT was significantly lower in the eyes of VKH group at 12 (246.58 ± 21.80 μm vs. 258.60 μm ± 15.61, p < 0.05) and 24 months visit (226.67 ± 14.21 μm vs. 253.15 ± 15.84 μm, p < 0.05). RNFL thickness was significantly higher in the eyes of VKH group at initial visit, 6 and 12 months follow‐up visit, but no significant difference between VKH group and control group at 24 months follow‐up visit (95.83 ± 14.85 μm vs. 97.14 ± 12.97 μm, p > 0.05).

Conclusions

There were significant changes of CMT and RNFL thickness in the eyes with VKH disease during 24 months follow‐up period. Detecting or monitoring diseases including glaucoma and neuro‐ophthalmic diseases, which affect the retinal thickness in VKH patients, we recommend to consider the longitudinal change of the retinal thickness.
The predictive value of retinal fixation for the visual outcome after anti‐VEGF treatment of diabetic macular oedema with center involvement
Authors: Stæhr Jakobsen N. , Ancher Larsen D. , Bek T.
Published: September 2016

Purpose

Diabetic macular oedema involving the foveal center can be treated with intra‐vitreal anti‐VEGF injections. However, the beneficial effect of this treatment is not unequivocal and presently no known parameter can differentiate patients who benefit by an improved visual acuity after the treatment from the patients who do not. Therefore, the present study aims to investigate the relation between visual acuity and retinal fixation area as a putative predictive parameter for the visual acuity after anti‐VEGF treatment in a planned prospective study.

Methods

60 eyes from 30 diabetic patients (mean age 61 years) with clinically significant macular oedema were subjected to examination of fixational eye movements before each of three monthly anti‐VEGF injections and at 1‐ and 4‐month follow‐up. Fixational eye movements were recorded for both eyes during binocular and monocular vision using a video based eye‐tracking system. The fixational saccades and the bivariate contour ellipse area (BCEA) were analyzed using standardized algorithms.

Results

The data from the baseline examination shows a linear correlation between best‐corrected visual acuity and the retinal fixation area estimated by the monocular bivariate contour ellipse area in the studied eyes (r2 = 0.21, p < 0.01).

Conclusions

Reduced visual acuity is followed by an increased fixation area in patients with diabetic macular oedema with center involvement. Prospective data will show whether the retinal fixation area can be used as a predictive parameter for the visual prognosis after anti‐VEGF treatment of diabetic macular oedema.
High resolution adaptive optics retinal image analysis in early‐stage central areolar choroidal dystrophy with a PRPH2 mutation
Authors: Gocho K. , Itoh N. , Akeo K. , Kameya S. , Hayashi T. , Takahashi H.
Published: September 2016

Purpose

To report clinical features in Japanese patients with early stage (stage 1 and 2) central areolar choroidal dystrophy (CACD).

Methods

Five family members participated in this study. We performed comprehensive ophthalmic examination, including adaptive optics (AO) retinal imaging. Mutation analysis of the PRPH2 gene was performed by Sanger sequencing. The protocol of this study conformed to the tenets of the Declaration of Helsinki and was approved by the Institutional Review Board of The Jikei University School of Medicine.

Results

Four family members possessed a heterozygous PRPH2 mutation (p.R172Q), however, a member with a mutation did not show any ophthalmological abnormality. Two patients showed mild parafoveal retinal dystrophy and reduction of cone density revealed by AO analysis.

Conclusions

We described a CACD family with marked intrafamilial phenotypic variations. Our results indicate that parafoveal cone photoreceptors are affected primarily at the early‐stage CACD.
Terrien marginal degeneration presenting with corneal perforation
Authors: Perez Navarro I. , Ascaso F. , Sánchez Marín J.I. , Almenara Michelena C. , Estebán Floría O. , Martínez Vélez M. , Idoate A. , Berniolles J. , Del Buey Sayas M.Á.
Published: September 2016

Purpose

Terrien marginal degeneration is a slow‐progressing, bilateral but asymmetric degeneration of the peripheral cornea. The spontaneous corneal perforation is rare. To report a imminent corneal perforation as a presenting sign Terrien marginal degeneration, treated with amniotic membrane implant.

Methods

A 70‐year‐old man presented with complaints of pain, redness,and decreased visión in the left eye (LE). Examination revealed peripheral corneal thinning 360º with superficial vascularization and secondary lipid keratopathy. There was an area of more thinning at the 5 o′clok position. His best‐corrected visual acuities (BCVAs) were 90°−4 + 4: 0.8 on the RE and 80°−3.75 + 4: 0.6 on the LE. Corneal topography with Orbscan of the LE revealed high oblique astigmatism with Sim K values of 48.75D at 140° and 43.25D at 50°. AS‐OCT showed corneal thinning and cavity formation with intact epithelial layer and affected endothelium in the thinned área.

Results

Due to the imminet corneal perforation was selected to make an amniotic membrane implant. Several circular layers of amniotic membrane rolled up on themselves and placed in the thinned área, fixing them with nylon 10‐0 suturing it to perilesional healthy cornea. The post‐operative AS‐ OCT reveals good adhesion of the amniotic membrane and corneal thickness recovery.

Conclusions

Terrien marginal degeneration is an unusual cause for a spontaneous corneal perforation. Patients with this disorder should be warned about this possibility. Surgery (lamellar graft, amniotic membrabe implant) can preserve corneal integrity and is indicated when conventional options fail to maintain vision or if perforation is imminent.