bluuebunny/crossref_metadata_2025 huggingface dataset:
Temporal macular ganglion‐cell inner plexiform layer thinning is a hallmark of early glaucomatous damage
Authors: Triolo G. , Monsalve P. , Feuer W.J. , Mwanza J.C. , Gedde S.J. , Parrish R.K. , Budenz D.L. , Vazquez L.E.
Published: September 2016

Purpose

To investigate the pattern of damage affecting the GCIPL and to compare it to the topographical RNFL thinning in early glaucoma (EG).

Methods

Total Average (Tot Avg) and quadrant (S, I, N, T) RNFL, Tot Avg and sector (ST, S, SN, IN, I, IT) GCIPL thicknesses were acquired with Cirrus SD‐OCT in 99 controls, 99 EG, and 50 severe glaucoma (SG) patients. S/I Avg and N/T Avg RNFL, T Avg and N Avg GCIPL thicknesses were also calculated. AUCs were obtained for each parameter. ANCOVA was used to study the changes occurring to couples of rNFL/GCIPL sectors according with VFMD. RNFL and GCIPL sectors were compared normalizing the raw values to their sector's dynamic range [the interval between mean sector thickness in controls (max) and minimum sector thickness in SG (floor)], using the following equation: (sector thickness–floor)/(max–floor). The relationship between VFMD and S RNFL/ST GCIPL or I RNFL/IT GCIPL normalized thicknesses was investigated with linear regression analysis.

Results

GCIPL and RNFL sectors were thinner in EG and SG than controls (ANOVA, p < 0.001). In the EG group T Avg GCIPL was thinner than N Avg GCIPL (p < 0.001). S/I Avg rNFL had a higher AUC compared to Tot Avg (p = 0.001) and N/T Avg rNFL (p < 0.001). Similarly, T Avg GCIPL had a higher AUC (0.936) compared to Tot Avg GCIPL (p = 0.019) or N Avg GCIPL (p < 0.001). T Avg and N Avg GCIPL slopes against VFMD were significantly different (p < 0.001) in EG (VFMD ≥–6 dB), but not in SG (VFMD <–6 dB, p = 0.79). In EG, the slopes against VFMD were not statistically different for ST GCIPL vs. S RNFL (p = 0.258) and for IT GCIPL vs. I RNFL (p = 0.164).

Conclusions

Temporal macular GCIPL thinning is a hallmark of early glaucomatous damage along with S/I peripapillary RNFL thinning. Conversely, nasal GCIPL sectors are relatively spared in EG, resembling a pattern of damage more typical of N/T peripapillary RNFL.
Retinal astrocytic hamartomas: 2 cases of atypical clinical presentation
Authors: Bouteleux V. , Tick S. , El Chehab H. , Mendes M. , Agard E. , Russo A. , Dot C.
Published: September 2016

Purpose

Retinal astrocytic hamartomas (RAH) are rare benign tumors found mainly in patients with phacomatosis. In these cases, RAH is a major diagnosis criteria.

Methods

We report the cases of two patients with 2 different clinical presentations.

Results

The case 1 is an asymptomatic man without medical history. A voluminous white retinal lesion is discovered incidentally. The ultrasound shows intratumoral calcifications and autofluorescence imaging shows hyperautofluorescent calcified beads. Characteristic moth‐eaten spaces are seen on the SD‐OCT. The final diagnosis is isolated RAH.

The case 2 is a 56 year old woman suspected of neurofibromatosis (NF) type 2. The fundoscopy found in both eyes a peripapillary whitish flat retinal lesion with blurred edges located on the surface of the retina. There is no autofluorescence nor hyperfluorescence. The diagnosis of plane RAH (= type 1) is made given the context.

Conclusions

RAH must be known because of the impact on phacomatosis diagnosis. RAH are associated with Tuberous Sclerosis Complex in about 55% of cases and with NF type 1 and type 2 in 15% of cases. Nevertheless in 1/3 of cases it occurs in healthy subjects. Three types of RAH have been described (plan (case 1), multinodular (case 2) and intermediate). Classical appearance (=type II) is a yellowish nodular ‘mulberry‐like’ tumor. It is autofluorescent and hyperfluorescent in late frames of angiography. However, there are less typical presentations which is reported in case 2 and which makes discuss differential diagnosis.

RAH can be a difficult diagnosis for which the clinical history and the multimodal imaging are essential. Neurological opinion and cerebral imaging should complete the investigation to search other diagnosis criteria of phacomatosis before concluding in an isolated form.
Evaluation of monotherapy of intravitreal Bevacizumab in retinopathy of prematurity stage 3 plus
Authors: Shirzadeh S.
Published: September 2016

Purpose

Evaluation of monotherapy of Bevacizumab intravitreal effect in Retinopathy Of Prematurity stage 3 plus treatment

Methods

158 eyes of 89 premature infants with threshold ROP 3 plus disease which 86 (51.2%) in zone I and 82 (48.8%) in zone II, were treated with intravitreal injection of 0.625 mg in 0.025 cc bevacizumab that 11eyes (7%) were treated with second injection. No prior laser or other intravitreal therapy was done. Fundus examination was performed prior to the intervention and at each follow‐up visit. Changes in various mean vital parameters 1 week post intervention compared to pre‐intervention were assessed.

Results

Any infant wasn't any problem post intravitreal bevacizumab injection. After 4–161 days (mean 17.62), all eyes showed complete traet the puls disease and after 4–278 days (mean: 44.39) all eyes showed complete retinal vascularisation without any signs of disease recurrence.

Conclusions

Treatment of ROP stage III puls disease with intravitreal Bevacizumab was effective in all cases and should be considered for treatment. Any side effect of Bevacizumab was seen. More patients with longer follow‐up duration are mandatory to confirm the safety and efficacy of this treatment.
Early hydroxychloroquine retinal toxicity enhanced by multifocal electroretinogram and laser flare‐cell meter
Authors: Cellini M. , Sebastiani S. , Campos E.
Published: September 2016

Purpose

The aim of this study is the evaluation of the multifocal electroretinogram (mfERG) and the laser flare‐cell meter methodology (LFM) in early detection of hydroxychloroquine (HCQ) retinal toxicity.

Methods

We enrolled 10 patients mean age 64.8 years with rheumatoid arthritis in therapy with hydroxychloroquine (400 mg/day) and cumulative dose (CD) of 625.6 ± 167.44‐g with no signs of retinal toxicity. As control group we recruited 10 health subjects mean age 61.3 years. MfERG (Retimax Plus, CSO, Florence, Italy) and LFM (FM‐500, Kowa, Tokio, Japan) were performed in all patients and controls. The Wilcoxon signed‐rank test and Spearman's correlation test was performed considering p < 0.05 as positive.

Results

Patients treated with HCQ showed compared to controls a significant amplitude reduction 0.518 ± 0.348 μV vs. 0.745 ± 0.337 μV (p = 0.035) with equally significant increase in latency 38.611 ± 2.857 ms vs. 36.334 ± 2.212 ms (p = 0.024) P1 wave in ring 2 of mfERG. The alteration of dependent values of mfERG correlated to the HCQ‐CD. To evaluate the behavior of the flare we divided the patients into two groups according to the CD: a group with CD > 500‐g and one with CD < 500‐g. The CD Group > 500‐g had a significant increase in flare values than the CD group < 500‐g: 14.4 ± 6.266 pg/ms vs. 8.1 ± 2.828 pg/ms (p = 0.008). The increase in the flare on the CD group>500 g was found to be related to the drug CD (r = 0.899; p = 0.001).

Conclusions

We found that mfERG P1 wave implicit time in ring 2 and the flare is the more sensitive test for demonstrating retinal dysfunction from HCQ toxicity in the setting of a normal fundus with a normal authomated visual field 10.2 and normal visual acuity. The increase in the flare would indicate not only a damage to the iris and cliary body pigmented cells but also an enzyme‐based breakdown of the blood retinal barrier directly caused by HCQ.
Case‐finding for angle closure: the diagnostic value of simple tests for estimating limbal and central anterior chamber depth
Authors: Dabasia P. , Murdoch I. , Edgar D. , Lawrenson J.
Published: September 2016

Purpose

To evaluate the diagnostic accuracy of limbal and central anterior chamber depth measurement for detecting gonioscopically narrow anterior chamber angles (ACAs).

Methods

A total of 78 subjects with narrow or open ACAs underwent an assessment of anterior chamber depth at the temporal limbus by estimating depth as a percentage of peripheral corneal thickness (van Herick test) by one examiner and just‐touching‐slit‐length measurements of the central anterior chamber depth (Smith's test) by a second examiner. Diagnostic performance was compared with (a) a gonioscopy reference standard, performed by a third examiner using the International Society of Geographical and Epidemiological Ophthalmology (ISGEO) definition of primary angle closure and (b) a classification based on clinical opinion of occludability. All examiners were masked regarding each subject's clinical status and other test results. Sensitivity, specificity, and partial area under the receiver operating characteristic curve (AUROC) were generated.

Results

The van Herick grading cutoff of 25% or less and ISGEO gonioscopic classification achieved 80% (95% CI 65–89) sensitivity and 92% specificity (95% CI 80–97) for narrow angle detection, with specificity reaching 97% (95% CI 87–100) for a cutoff of less than or equal to 15%. Notably, with a gonioscopic classification based on clinical opinion of occludability, van Herick (≤25%) together with Smith's test (≤2.50 mm) detected 100% of narrow angle subjects.

Conclusions

The van Herick test provides good discrimination between narrow and open angles both alone, and in combination with the measurement of central anterior chamber depth. These tests show good potential for identifying individuals who may benefit from further gonioscopic assessment in a case‐finding or screening setting.
Aberrations, accommodation and pseudoaccomodation in myopia and hyperopia
Authors: Tarutta E. , Harutyunyan S. , Khandzhyan A. , Khodzhabekyan N.
Published: September 2016

Purpose

A comparative study of accommodation, pseudoaccommodation and higher order optical aberrations (HOA) in young people with myopia and hyperopia

Methods

39 myopic eyes (averagely −5.2 ± 1.5 D) and 53 hyperopic eyes (averagely +3.1 ± 1.15 D) of 46 patients aged 5–20 years (mean age 11.6 ± 0.6 years) were examined. Objective accommodative response (OAR) was measured on Grand Seiko Binocular Open Field Auto ref/keratometer WR‐5100K. Aberrometry was conducted on OPD‐Scan III (Nidek). Relative accommodation reserve (RAR) were measured. The amplitude of pseudoaccomodation was determined as the difference between the calculated additional plus lens of 3.0 D and the power of the minimum plus lens which allowed reading in cycloplegic conditions (1% cyclopentolate hydrochloride × 2) at the distance of 33 cm.

Results

OAR and RAR were significantly higher in hyperopic patients (−2.2 ± 0.07 D and −3.0 ± 0.17 D; respectively), as compared to myopic ones (−1.8 ± 0.09 D, p < 0.01, and −2.2 ± 0.11 D, p < 0.05; resp.). Total HOAs measured with a pupil 4 mm wide: root mean square, vertical coma, spherical aberrations, as well as pseudoaccomodation were significantly higher in myopic patients (0.5 ± 0.05 D; −0.05 ± 0.01 D; 0.15 ± 0.05 D; 0.9 ± 0.1 D resp.) in comparison with those in hyperopic patients (0.37 ± 0.03 D; −0.003 ± 0.01 D; 0.04 ± 0.01 D; 0.6 ± 0.1 D resp., p < 0.05). Corneal spherical aberrations were measured to be 0.1 ± 0.03 D in myopic and 0.03 ± 0.04 D in hyperopic patients (p < 0.05).

Conclusions

OAR and RAR are lower in myopia compared with hyperopia. Root mean square and some HOAs are higher in myopia, which probably accounts for higher pseudoaccomodation values in myopic patients.
EDI‐OCT is less suited for close monitoring of primary stromal choroiditis when compared to Indocyanine green angiography
Authors: Herbort C.P. , Balci O. , Gasc A. , Jeannin B.
Published: September 2016

Purpose

Investigate the performance, utility, and precision, of enhanced depth imaging optical coherence tomography thickness (EDI‐OCT‐T), versus indocyanine green angiography (ICGA), in tracking any fluctuation in the activity of primary stromal choroiditis (PSC) in response to therapy during long‐term follow‐up.

Methods

Patients with a diagnosis of PSC; Vogt Koyanagi Harada (VKH) or birdshot retinochoroiditis (BRC), with untreated initial disease with long‐term follow‐up including both ICGA and EDI‐OCT, were recruited at the Centre for Ophthalmic Specialized care, Lausanne, Switzerland. Angiography signs were quantified according to established dual FA and ICGA scoring systems for uveitis. Changes in ICGA score, and EDI‐OCT‐T, in response to therapy, were assessed.

Results

Among 1829 uveitis patients seen from 1995 to 2015, 59 patients (3.2%) were diagnosed with PSC of which 4 patients (2 BRC and 2 VKH) fulfilled the restrictive inclusion criteria. Mean EDI‐OCT‐T decreased from 672 ± 101 μm at entry to 358.5 ± 44.5 μm in a mean of 26.5 months at stabilization. Mean ICGA scores decreased from 28 ± 4.2 at entry, to 5 ± 7 at stabilization. Only ICGA was sufficiently sensitive and reactive to detect disease recurrencies and efficacy or absence of effect of successive treatment changes, detected in 7 instances during follow‐up, but not recorded by EDI‐OCT.

Conclusions

This pilot study showed that ICGA was the more sensitive methodology; able to promptly identify evolving subclinical and occult choroidal disease and flag occult recurrence and/or therapeutic responses that were otherwise missed by EDI‐OCT. Although EDI‐OCT‐T showed a linear decrease, these changes were too sluggish to be relied upon for close follow‐up and timely adjustment of therapy.
Eye position under general anesthesia in orthophoric children
Authors: Manoli P. , Auckburally M. , Jullienne R. , Thuret G. , Gain P. , Lebranchu P. , Pechereau A.
Published: September 2016

Purpose

The aim of this study is to evaluate the effect of general anesthesia with muscle relaxant on the horizontal ocular deviation in orthophoric children.

Methods

Children aged 4–16 years requiring a non‐ophthalmological surgical procedure under general anesthesia with neuromuscular blockade were included. Prior ophthalmological examination excluded any oculomotor disorder. Horizontal ocular deviation was measured by the Hirschberg photographic method by comparing pictures taken in the awakened state to those taken under general anesthesia. Monitoring of anesthesia was performed by the Bispectral index (BIS) and muscle relaxation by the train of four (TOF).

Results

33 Patients were included. Mean age was 8(±4) years and 67.7% were male. The mean horizontal ocular deviation after general anesthesia with neuromuscular blockade was −0.2 diopters (SD 9.7). Median was −0.7 diopters. 72.7% of patients had an ocular deviation of less than 7.5 diopters with a normal distribution.

Conclusions

Our results show that contrary to popular belief, eye position under general anesthesia in children without strabismus is not divergent but very close to orthophoria.
Selective retina therapy (SRT) for diabetes macular edema in Korean patients: 12‐months results
Authors: Park Y.G. , Roh Y.J.
Published: September 2016

Purpose

Selective Retina Therapy can induce proliferation and migration of retinal pigment epithelium (RPE) cells at SRT‐irradiated areas without damaging photoreceptor cells. We demonstrate 1‐year clinical results of SRT for clinically significant diabetic macular edema (DME) in Korean patients.

Methods

Prospective nonrandomized interventional case series study. Twenty‐three eyes of 21 patients with clinically significant DME were treated with SRT and followed up for 12 months. After analysis of the correlation between the RM value and FFA visibility, the sensitivity and specificity of reflectometry was calculated. We measured best‐corrected ETDRS visual acuity (BCVA). Microperimetry was employed to measure the macular sensitivity within the central 10° visual field, and the central macular thickness (CMT) and maximum macular thickness (MMT) were measured at every 3 months. Patients were considered for retreatment at 3 months if there was no decrease in CMT.

Results

Thirteen of 23 eyes were included for the analysis of 1‐year results. BCVA improved from 69.5 letters at baseline to 76.23 letters at 6 months and 71.3 letters at 1 year. Although change in CMT did not demonstrate a significant change at two‐time points, MMT were decreased from 446.7 ± 78.4 μm to 423.5 ± 76.5 μm, 408.5 ± 59.6 at 6 months, 12 months (all p < 0.05) and mean macular sensitivity were increased from 21.5 ± 3.1 dB to 22.9 ± 2.4 dB, 23.2 ± 2.5 dB respectively. (p = 0.009, p = 0.001). Additional SRT was performed for nine eyes (69.2%).

Conclusions

In 9 of 23 eyes (39.1%), BCVA was maintained or improved by SRT monotherapy during 1 year follow‐up period. The improvement in maximum macular thickness (MMT) and macular sensitivity support that SRT treatment could be effective and safe modality in Korean patients with clinically significant DME.
Effect of biochemical cues on proliferation, phenotype and migration of human corneal stromal cells
Authors: Fernández‐Pérez J. , Ahearne M.
Published: September 2016

Purpose

With the increasing demand for corneal replacements and a shortage of suitable donors, tissue engineering and cell based therapies have emerged as a possible solution. Understanding the influence that biochemical factors have on corneal wound healing is needed to improve tissue regeneration. Our aim was to investigate the effect of several molecules on human corneal stromal cells.

Methods

Corneal fibroblasts were serum‐starved for 72 h in DMEM/F12 and then exposed to specific reagents for 7–14 days. The reagents examined in this study were ascorbic acid (AA), retinoic acid (RA), FGF‐2, PDGF‐BB, IGF, TGF‐β1, TGF‐β3, IBMX and insulin‐transferrin‐selenium (ITS). Proliferation was assessed by AlamarBlue assay, general morphology was monitored by bright field microscopy and the expression of keratocan, ALDH3A1 and smooth muscle actin (α‐SMA) at the mRNA level was quantified by qPCR. Immunohistochemistry and western blotting were also performed to assess protein expression.

Results

AA, IGF‐1, RA and ITS increased the expression of keratocyte markers such as keratocan and ALDH3A1, while not increasing fibrotic/myofibroblast marker α‐SMA. FGF‐2 and PDGF‐BB decreased expression of keratocan and ALDH3A1 without up‐regulating α‐SMA, suggesting a fibroblastic phenotype. TGF‐β1 and TGF‐β3 were shown to up‐regulate α‐SMA expression but TGF‐β3 also up‐regulated keratocan. All reagents apart from AA resulted in an increase in cell proliferation by day 7.

Conclusions

This study demonstrates the influence different biochemical cues have on corneal stromal cells. These findings will be useful in developing the next generation of therapies for corneal diseases and injuries.
Influence of material compliance on human corneal stromal cell behaviour
Authors: Kelly C. , Ahearne M.
Published: September 2016

Purpose

Due to a shortage of healthy donor tissue, bioengineering strategies for corneal regeneration are drawing more attention. It is well established that substrate stiffness has an effect on the proliferation and phenotype of many cell types. In this study, we aim to investigate the influence of the mechanical environment on corneal cell behaviour, by demonstrating the effects of varying material stiffness on the growth and morphology of human corneal stromal cells.

Methods

Using blends of two commercially available polydimethylsiloxane (PDMS) elastomer kits, cured polymer substrates with elastic moduli ranging from 12 kPa to 3 MPa were achieved. Materials underwent tensile mechanical testing to 10% strain in order to determine elastic mechanical properties. Samples were coated with a thin layer of collagen I to promote cell adhesion.

Results

Contact angle measurements were taken before and after protein coating, with a decrease in angle from 90.30 ± 0.47° to 73.26 ± 2.24°, indicating a significant increase in hydrophilicity of the PDMS. Phase contrast imaging was used to visualise differences in morphology of cells seeded onto the substrates, while actin and DAPI (4′,6‐diamidino‐2‐phenylindole) staining were employed to view differences in cytoskeletal structure under confocal microscopy. Cells on softer substrates displayed increased proliferation, as determined by AlamarBlue assay, with a notably spread and elongated fibroblastic morphology. Stiffer substrates induced increased cell aggregates, with a more dendritic shape visible. Gene expression of cells was also monitored by qPCR, with observed upregulation of collagen I, ALDH3A1 and keratocan, which was more pronounced in cells seeded on less compliant substrates.

Conclusions

These results will be useful in future biomaterial scaffold designs for corneal tissue regeneration.
Comparison of retinal and choroidal involvement in sarcoidosis chorioretinitis
Authors: El Ameen A. , Herbort C.P.
Published: September 2016

Purpose

To assess the respective involvement of retina versus choroid in ocular sarcoidosis (OS) using dual fluorescein (FA) and indocyanine green angiography (ICGA).

Methods

Retrospective study on patients with the diagnosis of OS seen in the Centre for Ophthalmic Specialized Care, Lausanne, Switzerland. The diagnosis of OS was based on a compatible uveitis associated with a positive biopsy, or positive broncho‐alveolar lavage, or bilateral hilar lymphadenopathies or 2 of the 3 following laboratory test including elevated lysozyme, elevated angiotensin converting enzyme or elevated polyclonal activation, together with a negative quantiferon‐TB Gold test. Angiography signs were quantified according to an established FA and ICGA scoring system for uveitis (Int Ophthalmol. 2010;30:539–52 and Ocul Immunol Inflamm 2010;18:385–9).

Results

Among 1,325 uveitis patients seen from 2000 to 2015, 23 patients (4 men) fullfilled the diagnostic criteria and could be included in the study. The choroid was predominantly involved in 19 patients (82.6%) and the retina in 4 patients (17.4%). The mean angiographic score was 7.3 ± 4.6 for the retina versus 14.2 ± 5.1 for the choroid (p < 0.0001). In 3 of 23 patients (13%), FA did not show retinal inflammation while ICGA was strongly positive, showing occult choroidal lesions.

Conclusions

This study shows for the first time the respective involvement of retina and choroid in OS. Choroid is preferentially involved for which ICGA is the examination of choice. By looking only at FA, there is a risk of underestimating global ocular involvement and to miss choroidal involvement. To evaluate correctly intraocular inflammation in OS and to have a better follow‐up, the use of dual FA & ICG angiography is recommended.
Ocular candidiasis in intravenous drug misusers
Authors: Lam D. , Belazzougui R. , Fardeau C. , Touitou V. , Le Hoang P. , Edel Y. , Bodaghi B.
Published: September 2016

Purpose

To study the characteristics, the management and evolution of Candida endophthalmitis among intravenous drug misusers in the era of new systemic antifungal agents.

Methods

Retrospective, descriptive study of patients with ocular candidiasis performed at Pitié‐Salpêtrière hospital, Paris, France, from 2002 to 2015.

Results

12 patients (14 eyes) had fungal endophtalmitis associated with drug misuse. Mean age at diagnosis was 41.1 years old and 83% of patients were male. Misuse of buprenorphine and morphin sulfate were noted in 83 and 17% respectively. 50% had polymedications. The way of infection was 50% hand transmission and 50% salivary transmission. Many of them had systemic co‐infections: hepatitis B, C, D or Human Immunodeficiency Virus. Patients presented with chorioretinitis (50%), endophthalmitis (57%) or both (36%). The microbiological diagnosis was obtained from anterior chamber tap (50%), vitrectomy (57%), skin, hair or mouth sample (7% each). 36% of the samples were positive and gave a fungal identification (75% positive for Candida albicans; 25% positive for Candida tropicalis and dubliniensis). At diagnosis of endophtalmitis, mean visual acuity was 0.9 log MAR and 0.3 logMAR after resolution of endophthalmitis. Patients received fluconazole (50%), voriconazole (42%) or amphotericin B (8%), associated with intravitreal injections of amphotericin B (50%) or vitrectomy (50%). Mean time of treatment was 2 months.

Conclusions

Fungal endophthalmitis is a sight‐threatening disease most commonly caused by Candida species. It is important to maintain a high index of suspicion of Candida ocular infection, particularly among intravenous drug users, even if they have drug substitution. Infection is mostly due to the preparation process. An early treatment based on antifungal agents highly improve the visual prognosis.
Prevalence and incidence of epimacular membranes in patients with wet AMD
Authors: Ricouard F. , Foveau P. , Zimmermann A. , Conart J.B. , Gaucher D. , Saleh M.
Published: September 2016

Purpose

The purpose of this study was to report the prevalence of epimacular membranes (ERM) in a population followed for age‐related macular degeneration (AMD) and to assess their incidence of onset over time.

Methods

Multicentric study of the EAST group (Eastern French Studies and Trial Group) (3 sites: Besancon, Nancy, Strasbourg) from the Vitreo‐macular interface in the Age‐related macular degeneration study (EVA study). All patients had consecutive control visits with Spectral‐Domain OCT (Spectralis, Heidelberg Engineering, Heidelberg, Germany). The OCT protocol consisted of the acquisition of horizontal cross‐sectional scans passing through the fovea and 3 and 6 mm of either side. The vitreomacular interface has been described according with the IVTS nomenclature.

Results

312 patients with one or both eyes treated for wet AMD (410 eyes) were studied. The average age was 80 years (55–96 year). The mean follow‐up was 30 months (2.9–110). 17.3% of eyes treated displayed an ERM at baseline and 18.8% at the end of follow‐up. During follow‐up, 13 eyes treated (3.2%) have developed ERM. 18% of eyes in the wet AMD group displayed an ERM against 10% of the eyes in the control group (190 fellow controled eyes), (OR = 2.08 CI95% = 1.22–3.49). Final visual acuity (VA) was significantly lower in patients with ERM (p < 0.01) with an average of 44.3 ETDRS letters against 52.6 in patients without ERM. The average number of IVI in patients with ERM was not significantly higher (p > 0.05). 17 patients (4.1%) with ERM underwent vitreoretinal surgery, with an average gain of 8.3 ± 18.4 letters.

Conclusions

Epiretinal membranes are frequent in patients treated for wet AMD and are associated with a lower VA. Nevertheless, they do not imply a higher need of injections. A study to assess the benefit of ERM surgery in patients with AMD is currently conducted.
Hemodynamic changes in eyes with early primary open‐angle glaucoma measured by transpalpebral rheoophthalmography
Authors: Kleyman A. , Kiseleva O. , Iomdina E. , Bessmertny A. , Luzhnov P. , Shamaev D.
Published: September 2016

Purpose

To evaluate the hemodynamic parameters in eyes with primary open‐angle glaucoma (POAG) and early glaucomatous visual field defects (early nasal step) using transpalpebral rheoophthalmography (TR).

Methods

Two groups of subjects were examined. Group 1 consisted of 56 eyes of 39 patients aged 57–79 (ave. age M ± σ = 67.33 ± 6.78) with POAG and early nasal step. Of these, 17 patients had POAG in both eyes. Group 2 consisted of 54 eyes of 27 patients aged 56–73 (ave. age 63.96 ± 5.54) without any eye pathology except initial cataract. Patients with any other optic disc or macular pathology, previous intraocular surgery, ocular trauma, or severe somatic pathology, were excluded from the study. All subjects underwent complete ocular and visual field examination, Goldmann intraocular pressure (IOP) measurement and TR. TR signals were registered using a specially designed tetrapolar lead system. Signal processing of TR with special software allowing automated analysis included three basic parameters: the rheographic index (RI), the period of maximum filling (PMF), and the indicator of the elastic modulus (IEM).

Results

The measured IOP was 16.9 mmHg (±1.7) in group 1 and 14.6 mmHg (±2.1) in group 2. A statistically significant difference was observed between the average RI (mΩ): for group 1 (M ± σ = 14.76 ± 3.18) vs. group 2 (26.44 ± 3.31), p < 0.05. A slight increase in the values of other parameters in group 1 (PMF = 21 ± 3 cs, IEM = 26 ± 4 cs) as compared to group 2 (PMF = 19 ± 3 cs, IEM = 24 ± 4 cs) was observed. This may be associated with a decrease in elasticity of intraocular blood vessel walls and their sclerotic changes.

Conclusions

The proposed new TR method is easy to use, highly informative and sufficiently accurate, allowing to objectively assess the changes of ocular hemodynamics, and facilitating the diagnosis of glaucoma at an early stage.
Evaluation of progressive visual dysfunction and degeneration of the retinal nerve fiber layer and macular thickness in patients with Parkinson disease
Authors: Satue M. , Rodrigo M.J. , Obis J. , Cipres Alastuey M. , Vilades E. , Garcia‐Martin E.
Published: September 2016

Purpose

To quantify changes in visual function parameters, in the retinal nerve fiber layer (RNFL) and macular thickness of patients with Parkinson disease (PD) over 5 years.

Methods

Thirty patients (60 eyes) with EP and 30 healthy subjects (60 eyes) underwent a complete ophthalmic evaluation, including assessment of visual acuity (VA) with ETDRS chart, contrast sensitivity vision (CSV) with Pelli Robson and CSV 1000E tests, color vision with Farnsworth and Lanthony D15 tests and retinal evaluation using Spectral domain Optical coherence tomography (SD‐OCT). All subjects were reevaluated after 5 years to quantify changes in visual function parameters, the RNFL and macular thickness.

Results

Changes were detected in visual function parameters (VA, CSV and Lanthony color indexes; p < 0.05) and RNFL thickness (inferotemporal, superotemporal and temporal sectors; p < 0.001) in PD patients compared to controls. Greater changes in VA, CSV and color vision (p < 0.05) were detected during the follow‐up in the PD group compared to healthy subjects. Greater loss of the RNFL (superotemporal and temporal sectors; p < 0.001) and macular thickness (all sectors except inner superior and inner inferior sectors, p < 0.001) was observed in the patients group after the 5‐year follow‐up.

Conclusions

Progressive visual dysfunction, macular thinning and axonal loss can be detected in PD patients. Analysis of the macular thickness and the RNFL by SD‐OCT can be useful for evaluating PD progression.
Measuring scleral thickness with optical coherence tomography in osteogenesis imperfecta: a case report
Authors: Brehon A. , Jullienne R. , Kaspi M. , Perrot J.L. , Grivet D. , Peoc'h M. , Gain P. , Thuret G.
Published: September 2016

Purpose

The blue sclera appearance is a distinctive but non‐specific clinical sign for osteogenesis imperfecta (OI), a connective tissue disorder caused by an abnormality of type I collagen. It is a challenging diagnosis because multiple bone fractures, occurring in early childhood, can be the only sign of the non‐lethal forms of OI. In these situations, differential diagnosis with child abuse is a major concern for Pediatricians. Aim: to investigate the scleral optical coherence tomography (OCT) and thickness measurement as a diagnostic test for OI.

Methods

The sclera of a 28‐year‐old man affected by a mild form of OI and presenting a blue scleral hue was examined with the sclera mode coupled with the enhanced depth imaging of the spectral domain OCT equipped with the anterior segment module device (SD‐ASOCT) (Heidelberg Engineering GmbH, Heidelberg, Germany). The scleral thickness was measured at a distance of 2000 μm from the scleral spur in eight meridians. Three measurements in each meridians were averaged and the mean and the standard deviation of the eight meridians were calculated. The examination of an age matched healthy volunteer served as a control.

Results

The mean scleral thickness of the OI patient was lower than that of the healthy patient, 277 μm ± 43 μm vs. 470 μm ± 50 μm. The superotemporal meridian was the thinnest in both patients.

Conclusions

These findings are consistent with the pathologic features previously described. The blue color results from the visualization of the underlying choroid through the translucent and thinner sclera. The in vivo scleral thickness measurement is a rapid and non‐invasive diagnostic tool that may be useful for challenging cases, especially in children with multiple fractures.
Ca2+ activity during ATP‐induced tone changes in porcine retinal arterioles in vitro spreads along the processes of perivascular cells
Authors: Kudryavtseva O. , Bek T.
Published: September 2016

Purpose

Recently, a novel population of perivascular cells (PVC) located immediately external to the vascular smooth muscle cells of retinal arterioles has been identified. These cells display Ca2+ activity simultaneously with tone changes of retinal arterioles and have processes extending into the retina. This data suggests that PVCs could play a role in the neurovascular coupling in the retina. The aim of the study was to investigate Ca2+ signals in PVCs and their processes during successive contraction and relaxation of retinal arterioles induced by ATP.

Methods

First order porcine retinal arterioles with preserved perivascular retinal tissue were mounted in a confocal myograph and loaded with the Ca2+‐sensitive fluorophore Oregon Green. The arterioles were preconstricted with 5*10‐8 – 10‐6 M U46619 and after the addition of ATP (10‐4 M) intracellular fluorescence from the PVC layer was recorded by a confocal microscope simultaneously with the vascular tone.

Results

ATP induced a biphasic tone response in 19% (5 out of 26) of the studies arterioles. The tone response consisted of 15 ± 4% initial contraction followed by 30 ± 20% relaxation. ATP induced Ca2+ waves in 49 ± 16% PVCs and 46 ± 14% processes during the contraction and in 46 ± 16% PVCs and 46 ± 14% processes during the relaxation. There was no significant difference between the frequency of Ca2+ waves in PVCs and their processes during contraction and relaxation (p > 0.05), but the amplitude of Ca2+ waves was significantly higher (p < 0.01) during contraction than during relaxation in the two structures.

Conclusions

PVC Ca2+ waves associated with contraction and relaxation of porcine retinal arterioles spread along cellular processes. The amplitude of Ca2+ waves in PVCs and their processes can be used to differentiate contracting and relaxing responses of retinal arterioles.
Application of laser radiation exposed Chlorpromazine for the treatment of pseudotumours induced in rabbit eyes
Authors: Popa Cherecheanu A. , Tozar T. , Geamanu A. , Iancu R. , Duta S. , Pirvulescu R.
Published: September 2016

Purpose

Multiple drug resistance (MDR) is a challenge that requires a flexible approach to find medicines able to overcome it. Among the methods used to overcome it, there is the exposure of existing medicines to UV laser beams to generate active photoproducts against bacteria and/or malignant tumors.

Methods

We studied the interaction of UV activate Chlorpromazine (CPZ) (irradiated with 266 nm pulsed laser beams), at concentrations of 10 and 20 mg/ml in ultrapure water, with rabbit eyes pseudotumors.

Results

The use of CPZ water solution exposed to 266 nm in the treatment of pseudotumor tissues produced on rabbit eyes shows that treatment results depend on initial (before irradiation) CPZ concentration and exposure time. At this stage, one may not specify which out of the generated photoproducts, individual or as a group, is/are efficient in pseudotumor cure but overall effects are observable. Application of CPZ irradiated solutions on rabbit eyes pseudotumors seems to produce a faster recovery of tissues with respect to control, untreated eyes.

Conclusions

Histologic findings in the treated tissues show a good antiinflamatory response. The results obtained open perspectives to fight MDR and/or development of pseudotumoral processes with substances that were not initially made for this purpose (non‐antibiotics, for instance).
Retinal α‐synucleinopathy: taking a new look at Parkinson's disease
Authors: De Groef L. , Normando E.M. , Andries L. , Davis B. , Lefevere E. , Van den Haute C. , Baekelandt V. , Cordeiro M.F. , Moons L.
Published: September 2016

Purpose

Although it is well‐documented that many patients with Parkinson's disease (PD) present with visual disabilities, scientific research has largely neglected the relation between PD and retinal dysfunction. A profound understanding of the retinal manifestations of PD, however, would not only help to gain new insights into its pathogenesis, it would also open up new avenues to improved disease management. Therefore, we have set out a comprehensive study to map retinal changes in several rodent models of PD/α‐synucleinopathy.

Methods

Two established models of PD/α‐synucleinopathy were used, i.e. the rotenone‐induced PD model in rats and a Thy1‐aSYN transgenic mouse line. In addition, a novel mouse model for the study of α‐synucleinopathy in the retina, based on local, viral vector‐mediated overexpression of α‐synuclein, was developed. Retinal neurodegeneration was studied via (i) in vivo imaging with optical coherence tomography and DARC (detection of apoptotic retinal cells); (ii) vision‐guided behavior tests; and (iii) (immuno) histological stainings for dopaminergic neurons (tyrosine hydroxylase), Lewy bodies (α‐synuclein, thioflavin) and apoptosis (cleaved caspase‐3), combined with specific retinal cell markers.

Results

Our results suggest that retinal changes related to PD/α‐synucleinopathy can be identified non‐invasively in these animal models and monitored over time. Moreover, histological analysis points out that specific retinal cell populations are affected, and that retinal changes precede PD manifestations in the brain.

Conclusions

This study brings together the first comprehensive data set on retinal manifestations in rodent models of PD/α‐synucleinopathy, and provides novel conceptual insights to support the idea that changes in retinal function/morphology can be used as early biomarkers for diagnosis and evaluation of treatment.
Therapeutic potential of non‐viral MRNA delivery to Müller cells for neuroprotection
Authors: Devoldere J. , Peynshaert K. , De Smedt S. , Remaut K.
Published: September 2016

Purpose

Retinal cell degeneration is a leading cause of vision loss in many ocular diseases. The progressive loss of retinal cells is often hereditary, but rarely monogenic. This enormous diversity in disease‐inducing mutations has hampered the development of gene replacement strategies to prevent or reverse retinal degeneration. Therefore interest has augmented for a treatment strategy that halts the degeneration process, rather than correcting the initial causative mutation. This work aims to evaluate the potential of chemically modified mRNA as a therapeutic strategy to stimulate neuronal survival and save vision, regardless of the initial genetic defect.

Methods

Evaluation of mRNA delivery to Müller cells was conducted in MIO‐M1 cells, using modified and unmodified reporter mRNA encoding the Green Fluorescent Protein (GFP). Lipid‐based vectors carrying the mRNA were delivered to Müller cells via serum‐containing medium or injected into fresh bovine vitreous, applied on top of the cells. In both setups uptake, level and duration of eGFP expression and toxicity of the lipoplex formulations were evaluated. In addition, the suitability of these complexes for intravitreal injection was assessed by measuring their mobility in bovine vitreous on a single‐particle level.

Results

Overall transfection levels are decreased in presence of vitreous, indicating that the vitreous is an important barrier for non‐viral mRNA delivery to the retina. Chemical modification of the mRNA substantially increased eGFP expression in >80% of cultured Müller cells.

Conclusions

Our data demonstrate that non‐viral lipid based carriers show good potential to transfect Müller cells in vitro. However, to make these mRNA therapeutics suitable for ocular targets, development of strategies to overcome the vitreal barrier will be crucial to implement ocular mRNA therapy in the future.
Pseudodominance in a Czech family with Usher syndrome type II
Authors: Kousal B. , Dudakova L. , Skalicka P. , Bujakowska K. , Liskova P.
Published: September 2016

Purpose

Usher syndrome is an autosomal recessive genetically heterogeneous disorder with congenital sensorineural hearing impairment and retinitis pigmentosa developing in late childhood and adolescense. We have identified a Czech family not aware of consanguinity with four members in two subsequent generations clinically diagnosed with Usher syndrome type II. The major aim of our study was to determine the disease‐causing mutation(s) in this family.

Methods

As an initial approach Sanger sequencing of USH2A exons 6, 7, 11, 13, 20, 61 was performed in the proband, followed by next‐generation sequencing of a panel testing 286 genes known to cause various inherited ocular disorders. Available relatives were screened by Sanger sequencing for the detected mutations. 1,161 population specific controls were used to check for allele frequencies of the identified sequence variants.

Results

The proband was found to harbour compound heterozygous mutations c.11864G>A; p.(Trp3955*) and c.13342_13347del; p.(Asp4448_Ser4449del) in USH2A while her affected daughter and son were homozygous for the c.11864G>A mutation. Segregation analysis confirmed that father of the affected children was a heterozygous carrier of the USH2A c.11864G>A. Affected brother of the proband was not available for our investigation. Mutation c.11864G>A has been previously observed in patients with Usher syndrome type II. Geographical origin in a particular region in Moravia was noted for parents of both the affected proband and her spouse. None of the two mutations were detected in Czech controls.

Conclusions

Pseudodominance may occur in outbred families. The estimation of the chance that a person will be a heterozygote carrier of a recessive disorder needs to be implemented into counselling. Geographic distribution of pathogenic alleles may display regional differences.
Phenotype of maculopathy in primary hyperoxaluria type 1
Authors: Derveaux T. , Delbeke P. , Walraedt S. , Raes A. , Van Laecke S. , Leroy B.P. , De Zaeytijd J.
Published: September 2016

Purpose

To describe the structural and functional characteristics of oxalate retinopathy, an entity described in only 40 cases until now.

Methods

Five patients with molecularly confirmed primary hyperoxaluria type 1 were subjected to multimodal retinal imaging (spectral‐domain optical coherence tomography, white light, and HRA multispectral imaging) and functional testing, including color vision testing, Goldmann perimetry, and ISCEV standard electrophysiological testing.

Results

One patient with a c.[33dupC]; c.[731T > C] mutation showed bilateral perifoveal retinal pigment epithelium hyperplasia. The fundus in the four other patients, all of whom share an identical homozygous c.[33dupC] mutation, ranged from normal to bilateral widespread distribution of retinal crystals and confluent macular retinal pigment epithelium hyperplasia with subfoveal fibrosis. All patients who had developed end‐stage renal disease showed some sign of retinopathy, more severe with earlier onset.

Conclusions

Retinopathy in primary hyperoxaluria type 1 shows considerable interindividual variation. No correlation between genotype and retinal phenotype was detected. A proposed clinical grading system of oxalate maculopathy derived from a literature review may help clinicians in estimating not only current visual function but also prognosis in this patient population that largely consists of preverbal infants.
Maculopapillary analysis in the posterior pole in patients with mild Alzheimer's disease
Authors: Salobrar‐Garcia E. , Garcia Y. , Lostao C. , Jañez L. , de Hoz R. , Rojas B. , Salazar J.J. , Ramirez A.I. , Gil P. , Yubero R. , Triviño A. , Ramirez J.M.
Published: September 2016

Purpose

To correlate the thickness of focal regions of the macula with those of the peripapillary nerve fiber layer using optical coherence tomography (OCT) in mild Alzheimer's disease (AD) patients and to compare them with age‐matched controls.

Methods

OCT of the macula and of the optic nerve from 19 mild AD patients and 25 control patients were included in the study. The thickness of 36 macular voxels of the 6 × 6 grid considered for analysis was correlated with the thickness of the 7 temporal papillary wedges across subjects. Each macular voxel was labeled with the peripapillary wedge with the highest correlation using a color‐coded map.

Results

In comparison with the controls, mild AD patients presented a significant: (i) thinning in the macular voxels 5, 6, 12, 15, 16, 18, 21, and 22 (p < 0.05) and; (ii) correlation between several macular voxels and some of the peripapillary wedges between groups (p < 0.05).

Conclusions

There were significant differences in the maculopapillary correlation map pattern between mild AD patients and control group. The OCT changes detected could be ascribed to the inflammation and neurodegeneration that occur in the early stages of AD and could serve as a basis for future research aimed to develop a quick, easy, and non‐invasive biomarker of AD.
Toward rational design of gene carriers: a novel ex vivo model to study the vitreoretinal interface as a barrier
Authors: Peynshaert K. , Fradot V. , Picaud S. , De Smedt S. , Remaut K.
Published: September 2016

Purpose

The vitreoretinal interface poses a serious hurdle for the retinal delivery of viral and non‐viral gene vectors after intravitreal injection. We have therefore developed a retinal model especially designed to study to which extent the ILM is a barrier for the penetration of vectors into the retina. In contrast to all existing explant models, ours is bovine‐derived and more importantly, the vitreous remains attached to the retina at all times to guarantee an intact vitreoretinal interface.

Methods

To investigate the influence of nanoparticle physicochemistry on their ability to penetrate the ILM we have injected various carboxylated polystyrene particles with a size range between 20 and 200 nm intravitreally in our model. After diffusion overnight the Müller cells are stained with Mitotracker Deep red and the nuclei with Hoechst. Finally, a z‐stack of confocal images of the retina is recorded using a water dipping objective that is brought into contact with the vitreous layer on top of the retina.

Results

Our data clearly illustrated that the ILM significantly hinders particle penetration into the retina. We also found that this penetration is greatly size‐dependent: the cut‐off for nanoparticles to cross the ILM lies between 40 and 100 nm. Intriguingly, the particles that did cross the ILM co‐localized solely with Müller cells, indicating these cells actively capture the nanoparticles out of the ILM and shuttle them into the retina.

Conclusions

In conclusion, we developed a model set‐up greatly mimicking human physiology to investigate the influence of particle physicochemistry on their ability to cross the ILM after intravitreal injection. This data collection will signify a leap forward in the rational design of gene vectors with the retina as their target, since this way their design can be tuned to actual in vivo requirements.