Evolution of macular atrophy in eyes with neovascular age-related macular degeneration compared to fellow non-neovascular eyes.

PURPOSE: Τo evaluate the evolution of macular atrophy (MA) in patients with neovascular AMD (nAMD), compared with their fellow eyes exhibiting dry AMD (dAMD). METHODS: This retrospective study included 124 patients from three centers treated with anti-VEGF in their nAMD eye and having dAMD in the fellow eye. Patients without MA at baseline were analyzed to study the time to first MA development. Synchronous and unsynchronous time course of MA was also studied. MA was evaluated using near-infrared images, while all available optical coherence tomography (OCT) images were used to confirm the criteria proposed by the Classification of Atrophy Meetings group for complete MA. RESULTS: MA first detection in nAMD eyes increased significantly from year 2 to 6 compared to dAMD eyes. Over the study's follow-up, 45.1% of nAMD-E developed MA, compared to 16.5% of fellow eyes (p < 0.001). When MA in the two eyes was compared in a synchronous paired manner over 4 years, nAMD eyes had an average MA progression rate of 0.275 mm/year versus 0.110 mm/year in their fellow dAMD eyes. Multivariate ANOVA revealed significant time (p < 0.001), eye (p = 0.003), and time-eye interaction (p < 0.001) effects. However, when MA did develop in dAMD eyes and was compared in an asynchronous manner to MA of nAMD eyes, it was found to progress faster in dAMD eyes (dAMD: 0.295 mm/year vs. nAMD: 0.176 mm/year) with a significant time-eye interaction (p = 0.015). CONCLUSIONS: In this study, a significant difference in MA incidence and progression was documented in eyes with nAMD under treatment, compared to fellow eye exhibiting dAMD. Eyes with nAMD tended to develop more MA compared to fellow dAMD eyes. However, when atrophy did develop in the fellow dAMD eyes, it progressed faster over time compared to MA in nAMD eyes.

Efficacy οf Wet Age-related Macular Degeneration Treatment οn Reading: A Pilot Study Using Eye-movement Analysis.

SIGNIFICANCE: Functional vision, as evaluated with silent passage reading speed, improves after anti-vascular endothelial growth factor (anti-VEGF) treatment in patients with wet age-related macular antidegeneration (wAMD), reflecting primarily a concomitant reduction in the number of fixations. Implementing eye movement analysis when reading may better characterize the effectiveness of therapeutic approaches in wAMD. PURPOSE: This study aimed to evaluate silent reading performance by means of eye fixation analysis before and after anti-VEGF treatment in wAMD patients. METHODS: Sixteen wAMD patients who underwent anti-VEGF treatment in one eye and visual acuity (VA) better than 0.5 logMAR served as the AMD group. Twenty adults without ocular pathology served as the control group. Central retinal thickness and near VA were assessed at baseline and 3 to 4 months after their first visit. Reading performance was evaluated using short passages of 0.4-logMAR print size. Eye movements were recorded using EyeLink II video eye tracker. Data analysis included computation of reading speed, fixation duration, number of fixations, and percentage of regressions. Frequency distributions of fixation durations were analyzed with ex-Gaussian fittings. RESULTS: In the AMD group, silent reading speed in the treated eye correlated well with central retinal thickness reduction and improved significantly by an average of 15.9 ± 28.5 words per minute (P = .04). This improvement was accompanied by an average reduction of 0.24 ± 0.38 in fixations per word (P = .03). The corresponding improvement in monocular VA was not statistically significant. Other eye fixation parameters did not change significantly after treatment. No statistically significant differences were found in the control group. CONCLUSIONS: Visual acuity tests may underestimate the potential therapeutic effects after anti-VEGF treatment in patients with relatively good acuity who are being treated for wAMD. Evaluating silent reading performance and eye fixation parameters may better characterize the effectiveness of therapeutic approaches in wAMD patients.

Isolated and Syndromic Retinal Dystrophy Caused by Biallelic Mutations in RCBTB1, a Gene Implicated in Ubiquitination.

Inherited retinal dystrophies (iRDs) are a group of genetically and clinically heterogeneous conditions resulting from mutations in over 250 genes. Here, homozygosity mapping and whole-exome sequencing (WES) in a consanguineous family revealed a homozygous missense mutation, c.973C>T (p.His325Tyr), in RCBTB1. In affected individuals, it was found to segregate with retinitis pigmentosa (RP), goiter, primary ovarian insufficiency, and mild intellectual disability. Subsequent analysis of WES data in different cohorts uncovered four additional homozygous missense mutations in five unrelated families in whom iRD segregates with or without syndromic features. Ocular phenotypes ranged from typical RP starting in the second decade to chorioretinal dystrophy with a later age of onset. The five missense mutations affect highly conserved residues either in the sixth repeat of the RCC1 domain or in the BTB1 domain. A founder haplotype was identified for mutation c.919G>A (p.Val307Met), occurring in two families of Mediterranean origin. We showed ubiquitous mRNA expression of RCBTB1 and demonstrated predominant RCBTB1 localization in human inner retina. RCBTB1 was very recently shown to be involved in ubiquitination, more specifically as a CUL3 substrate adaptor. Therefore, the effect on different components of the CUL3 and NFE2L2 (NRF2) pathway was assessed in affected individuals' lymphocytes, revealing decreased mRNA expression of NFE2L2 and several NFE2L2 target genes. In conclusion, our study puts forward mutations in RCBTB1 as a cause of autosomal-recessive non-syndromic and syndromic iRD. Finally, our data support a role for impaired ubiquitination in the pathogenetic mechanism of RCBTB1 mutations.

Mutations in CEP78 Cause Cone-Rod Dystrophy and Hearing Loss Associated with Primary-Cilia Defects.

Cone-rod degeneration (CRD) belongs to the disease spectrum of retinal degenerations, a group of hereditary disorders characterized by an extreme clinical and genetic heterogeneity. It mainly differentiates from other retinal dystrophies, and in particular from the more frequent disease retinitis pigmentosa, because cone photoreceptors degenerate at a higher rate than rod photoreceptors, causing severe deficiency of central vision. After exome analysis of a cohort of individuals with CRD, we identified biallelic mutations in the orphan gene CEP78 in three subjects from two families: one from Greece and another from Sweden. The Greek subject, from the island of Crete, was homozygous for the c.499+1G>T (IVS3+1G>T) mutation in intron 3. The Swedish subjects, two siblings, were compound heterozygotes for the nearby mutation c.499+5G>A (IVS3+5G>A) and for the frameshift-causing variant c.633delC (p.Trp212Glyfs(∗)18). In addition to CRD, these three individuals had hearing loss or hearing deficit. Immunostaining highlighted the presence of CEP78 in the inner segments of retinal photoreceptors, predominantly of cones, and at the base of the primary cilium of fibroblasts. Interaction studies also showed that CEP78 binds to FAM161A, another ciliary protein associated with retinal degeneration. Finally, analysis of skin fibroblasts derived from affected individuals revealed abnormal ciliary morphology, as compared to that of control cells. Altogether, our data strongly suggest that mutations in CEP78 cause a previously undescribed clinical entity of a ciliary nature characterized by blindness and deafness but clearly distinct from Usher syndrome, a condition for which visual impairment is due to retinitis pigmentosa.

Assessing Variability in Reading Performance with the New Greek Standardized Reading Speed Texts (IReST).

SIGNIFICANCE: This article evaluates the standardized Greek version of the International Reading Speed Texts (IReST) set, which enriches interlanguage comparisons and international clinical studies of reading performance. Moreover, it investigates how specific textual and subject-related characteristics modulate the variability of reading speed across texts and readers. PURPOSE: The purpose of this study was to develop a standardized Greek version of the IReST set and investigate how specific textual and subject-related factors modulate the variability of reading speed across texts and readers. METHODS: The English IReST texts were translated to Greek and matched for length, content, and linguistic difficulty. The Greek IReSTs were presented at a distance of 40 cm and size of 1 M to assess reading speeds of 25 normally sighted native speakers (age range, 18 to 35 years). The participants read the texts aloud while reading time was measured by stopwatch. Reading performance included measurement of reading speed in three units of analysis. Reading efficiency was assessed using a word-level oral reading task. Statistical analysis included evaluation of subject- and text-related variability, as well as correlations between reading speed and specific textual and subject-related factors. RESULTS: The average reading speed between texts was 208 ± 24 words/min, 450 ± 24 syllables/min, and 1049 ± 105 characters/min. Differences between readers accounted for the 76.6%, whereas differences across texts accounted for the 23.4% of the total variability of reading speed. Word length (in syllables per word) and median word frequency showed a statistically significant contribution to the variability of reading speed (r = 0.95 and 0.70, respectively). Reading speed was also statistically correlated with word reading efficiency (r = 0.68). CONCLUSIONS: The addition of the Greek version in the IReST language pack is expected to be a valuable tool for clinical practice and research, enriching interlanguage comparisons and international studies of reading performance.

Photoacoustic imaging methodology for the optical characterization of contact lenses.

We demonstrate photoacoustic microscopy as a metrology method for the optical characterization and quality control of contact lenses (CLs). Dual-wavelength excitation is applied to CLs tinted on both sides with two thin ink layers, each of them possessing distinctly different optical absorption properties. Thus, the method is capable of measuring the elevation maps of both CL surfaces during two subsequent imaging sessions and extracting the CL thickness, curvatures, and dioptric power. We show that such an easily implementable technique provides robust, high-precision, cost-effective three-dimensional imaging and characterization of both rigid and soft CLs, which renders it highly favorable for a broad range of applications.

Pharmacokinetics and efficacy of intraocular flurbiprofen.

PURPOSE: Intravitreal delivery of non-steroidal anti-inflammatory drugs could be an effective way to treat macular edema caused by posterior segment inflammation. In this study, we evaluated the intravitreal bioavailability and anti-inflammatory efficacy of flurbiprofen in rabbit eyes. METHODS: For pharmacokinetics, 0.1 ml of 7.66 mg/ml flurbiprofen solution was injected intravitreally and vitreous drug levels were analyzed at specific time points using LC-MS technique. For efficacy, 100 ng lipopolysaccharide of E.coli was injected intravitreally in rabbits to induce inflammation. The animals were separated in three groups and received intraocular flurbiprofen, dexamethasone and PBS to serve as control. Complete ocular examination and total cell count in aqueous fluid were determined to evaluate the extent of inflammation. Eyes were then enucleated for histopathology analysis. The efficacy in the uveitis model was determined by clinical signs of inflammation, total leukocyte count and histology findings. RESULTS: No adverse events were observed during pharmacokinetic assessment. No signs of inflammation, hemorrhage or retina detachment were detected. The recovery of flurbiprofen from vitreous samples was 92.6%. The half-life of flurbiprofen was estimated to be 1.92 h with an elimination constant rate (K) of 0.36. Treatment with intraocular injections of flurbiprofen and dexamethasone significantly reduced total leukocyte count in a manner comparable to dexamethasone [reduction of 96.84% (p < 0.05) and 97.44% (p < 0.05), respectively]. Histologic studies demonstrated significantly less signs of ocular inflammation after flurbiprofen injection compared to control eyes. CONCLUSIONS: Flurbiprofen is effective in suppressing inflammation in this experimental uveitis model. In our experimental setting, intravitreal flurbiprofen seem to have a therapeutic result comparable to dexamethasone. However, the half-life of the drug remains short, necessitating further research to prolong its presence in the vitreous cavity.

Silicone oil insulation effects on flash electroretinogram and visual evoked potential in patients with retinal detachment.

BACKGROUND: Silicone oil is used as endotamponade following vitreoretinal surgery to maintain the retina reattached when indicated. This study investigates the hypothesis that silicone oil causes insulation effects on the retina by affecting its response to light. METHODS: Electrophysiological responses to a flash stimulus were recorded using full-field electroretinography (ERG) and visual evoked potentials (VEP). Recordings were performed in 9 patients who underwent surgery for retinal detachment, before (1-2 days) and after (2-3 weeks) silicone oil removal (SOR) in both the study and the control eye. Flash ERG and VEP recordings were performed according to the ISCEV standard protocol. RESULTS: Statistically significant differences were found in the study eye in the amplitudes of the ERG responses and their corresponding ratios, i.e. the amplitude after SOR over the amplitude before SOR, in all conditions tested. No differences were observed in the control eye. The mean ratio of photopic ERG response was 3.4 ± 2.4 for the study and 1.0 ± 0.3 for the control eye (p<0.001). The mean ratio of ERG flicker response was 3.1 ± 2.4 and 1.0 ± 0.3, respectively (p = 0.003). Scotopic flash ERG ratio was 5.0 ± 4.4 for the study and 1.3 ± 0.6 for the control eye (p = 0.012). No differences were observed for the amplitude and latency of flash VEP response after SOR. CONCLUSIONS: Silicone oil causes a reduction in flash ERG responses; no effect was found on flash VEP responses. ERGs in eyes filled with silicone oil should not be considered representative of retinal functionality, in contrast to VEPs, which are not affected by silicone oil presence.

Xerophthalmia and acquired night blindness in a patient with a history of gastrointestinal neoplasia and normal serum vitamin A levels.

A 69-year-old male patient presented to our department with a 3-month history of nyctalopia. Reviewing of his general health revealed a history of gastrointestinal tumor treated with a modified WHIPPLE operation. Ocular findings at presentation included mild xerophthalmic features and nonspecific pigmentary retinal changes. A standard full-field electroretinogram (ERG) was obtained that showed normal photopic function and extinguished scotopic function. The ocular symptoms, the history and the ERG findings suggested vitamin A deficiency as a possible cause for his complaints. Serum vitamin A levels were subsequently requested, but the results were within normal limits. Despite the normal serum vitamin A levels, the patient was instructed to commence treatment with high doses of oral vitamin A supplements. One month after the onset of the treatment, the patient reported that his visual function has significantly improved, while repeat ERG testing revealed that scotopic function has improved to normal levels. This case highlights that in patients with acquired night blindness due to vitamin A deficiency, the ERG responses possibly represent a more sensitive marker compared to the serum levels of vitamin A.

Effect of panretinal photocoagulation treatment on vision-related quality of life of patients with proliferative diabetic retinopathy.

PURPOSE: To evaluate the effect of laser panretinal photocoagulation for bilateral proliferative diabetic retinopathy on vision-related quality of life. METHODS: In this prospective study, 20 patients (12 men and 8 women) with bilateral proliferative diabetic retinopathy treated with panretinal photocoagulation were included (mean age: 65 years, SD: 11.6 years). On average, patients received 2,140 laser spots per eye. The National Eye Institute 25-Item Visual Function Questionnaire (VFQ-25) was used to evaluate patients' vision-related quality of life. The VFQ-25 was filled in by interview twice, at the beginning and at least 1 month after the completion of panretinal photocoagulation. Comparison of preoperative and postoperative VFQ-25 composite and subscale scores was performed. Correlation was evaluated between change in composite score and treatment intensity as indicated by mean number in laser spots. RESULTS: Mean composite score before laser treatment was 71.9 ± 14.8 and after treatment it was 70.6 ± 17.2 (P = 0.748, paired t-test). None of the subscale scores had a statistically significant difference before and after treatment. Composite score change was not correlated with treatment intensity. CONCLUSION: Panretinal photocoagulation as applied in our study, although destructive in nature, is well tolerated by the patients, without interfering significantly with their quality of life.

Comparison of visual acuity charts in young adults and patients with diabetic retinopathy.

PURPOSE: To compare visual acuity (VA) assessed in healthy eyes and eyes with diabetic retinopathy (DR) using three different logMAR charts: the Sloan letter European-wide chart, the tumbling E chart, and the Landolt C chart. METHODS: Measurements on one eye of 40 volunteers (aged 29 ± 4 years) without visual impairment and 31 DR patients (aged 70 ± 9 years) with mild/moderate visual impairment were included. Visual acuity was assessed, with habitual refractive correction, using each of the three charts. Bland-Altman charts were constructed, and 95% limits of agreement were calculated to measure agreement. RESULTS: Mean VA in the group of young adults was -0.05 ± 0.10 (Sloan letter), -0.02 ± 0.13 (tumbling E), and 0.00 ± 0.12 (Landolt C) logMAR. Average VA estimates differed to a statistically significant extent between all charts. Mean VA in the DR group was 0.46 ± 0.25 (Sloan letter), 0.48 ± 0.26 (tumbling E), and 0.59 ± 0.28 (Landolt C). A statistically significant difference was observed for average Sloan letter versus Landolt C (p < 0.001) and tumbling E versus Landolt C (p < 0.001) acuities. Moreover, in healthy eyes, a moderate correlation (r = -0.38, p = 0.015) was found between the discrepancy in Sloan letter and Landolt C acuity and the mean VA estimate. The 95% limits of agreement were wide (more than approximately 0.2 logMAR for each comparison) and wider in the DR group chart comparisons than in healthy eyes. CONCLUSIONS: Landolt C charts resulted in worse VA estimates compared with letter and tumbling E charts in both young adults and visually impaired subjects with DR. These differences seem more pronounced in DR patients who exhibit worse VAs. The specific study population must be considered in comparing outcomes from different clinical practices.

Contrast sensitivity in the 'good eye' of adult patients with severe impairment in the other eye.

PURPOSE: It is widely accepted that monocular deprivation results in improved visual performance in the non-pathological eye. The current study investigates the effect of deprivation due to severe impairment in one eye during late childhood or adulthood, on the spatial performance of the fellow 'good' eye. METHODS: Twenty patients (age: 29 ± 9 years) with severe visual impairment in one eye (visual acuity equal or worse than count fingers at 1 m), for a period longer than 2 years, participated in the study. Only patients with an age less than 50 years and monocular deprivation onset greater than 9 years were included. On the basis of the time of deprivation the patients were categorised into two subgroups: (i) long-past deprivation (N = 8, age 28 ± 8 years, 9-20 years of deprivation) and recent deprivation (N = 12, age 30 ± 11 years, 2-4 years of deprivation). Eighteen more participants (age: 28 ± 5 years) with normal binocular vision served as the control group. Best-corrected contrast sensitivity was evaluated using reversing (2 Hz) vertical sinusoidal gratings. Seven spatial frequencies (1, 2, 4, 8, 12, 16 and 24 c/deg) were tested. Performance of the control group was tested both monocularly (dominant eye) and binocularly. RESULTS: In normal subjects, binocular viewing improved contrast sensitivity on average by 4.2 dB (corresponding to a 70% improvement in contrast threshold) compared to monocular recordings. Average contrast sensitivity in subjects with impaired vision in one eye was found to be higher by 5.0 dB (corresponding to an 83% improvement in contrast threshold) compared with the dominant eye of the control group. The increase in sensitivity was independent of spatial frequency. No differences were observed between the two subgroups with recent and long-past deprivation. CONCLUSIONS: Notable improvement in contrast sensitivity was found in the non-pathological eye of patients with severe impairment in the other eye at an age after the "critical" period of visual development. These findings are consistent with growing evidence supporting functional changes as a result of altered experience or injury in the adult vision system.

Comparing silent reading performance for single sentences and paragraphs: an eye movement-based analysis.

CLINICAL RELEVANCE: Reading performance in clinical practice is commonly evaluated by reading 'aloud' and 'as fast as possible' single sentences. Assessing comprehensive silent reading performance using passages, composed of multiple sentences, is the preferred reading mode in real-life reading conditions. BACKGROUND: The purpose of this study was to compare eye movement-based silent reading performance for standardised short sentences and paragraphs. METHODS: A group of 15 young volunteers (age range: 22-36 years) read silently and comprehensively in two sessions: (a) a paragraph with continuous text and (b) standardised short sentences. Text print size was 0.4 logMAR (1.0 M at 40 cm distance). Eye movements during reading were recorded using video oculography (EyeLink II, SR Research Ltd). Data analysis included computation of reading speed, fixation duration, the number of fixations, saccadic amplitude and percentage of regressions. Moreover, frequency distributions of fixation durations were analysed with ex-Gaussian fittings. RESULTS: Repeatability coefficient in silent reading speed was found better for the paragraph (66 wpm) than for short sentences (88 wpm). The superiority in repeatability coefficient for the corresponding eye movement parameters, i.e. fixation duration (35 vs 73 ms), regressions (10.1 vs. 22.3%) and fixations per word (0.21 vs. 0.37 fpw), was even more pronounced. In addition, a statistically significant improvement with the paragraph was found in average fixation duration (19 ± 26 ms, p = 0.02), regressions (4.2 ± 7.0%, p = 0.04) and ex-Gaussian fixation parameter, τ (82 vs. 111 ms). No statistically significant difference was found between average reading speed with the paragraph (220 ± 59 wpm) and the short sentences (206 ± 57 wpm) (p = 0.11). DISCUSSION: Due to their superior repeatability, paragraphs are preferable to short sentences when evaluating silent comprehensive reading. The concurrent recording of eye movement parameters in silent reading further improves variability and could offer an efficient measure of reading performance and a reliable biomarker of visuo-motor function.

Assessment of a Novel Semi-Automated Algorithm for the Quantification of the Parafoveal Capillary Network.

Introduction: We present a novel semi-automated computerized method for the detection and quantification of parafoveal capillary network (PCN) in fluorescein angiography (FA) images. Material and Methods: An algorithm detecting the superficial parafoveal capillary bed in high-resolution grayscale FA images and creating a one-pixel-wide PCN skeleton was developed using MatLab software. In addition to PCN detection, capillary density and branch point density in two circular areas centered on the center of the foveal avascular zone of 500µm and 750µm radius was calculated by the algorithm. Three consecutive FA images with distinguishable PCN from 56 eyes from 56 subjects were used for analysis. Both manual and semi-automated detection of the PCN and branch points was performed and compared. Three different intensity thresholds were used for the PCN detection to optimize the method defined as mean(I)+0.05*SD(I), mean(I) and mean(I)-0.05*SD(I), where I is the grayscale intensity of each image and SD the standard deviation. Limits of agreement (LoA), intraclass correlation coefficient (ICC) and Pearson's correlation coefficient (r) were calculated. Results: Using mean(I)-0.05*SD(I) as threshold the average difference in PCN density between semi-automated and manual method was 0.197 (0.316) deg-1 at 500µm radius and 0.409 (0.562) deg-1 at 750µm radius. The LoA were -0.421 to 0.817 and -0.693 to 1.510 deg-1, respectively. The average difference of branch point density between semi-automated and manual method was zero for both areas; LoA were -0.001 to 0.002 and -0.001 to 0.001 branch points/degrees2, respectively. The other two intensity thresholds provided wider LoA for both metrics. The semi-automated algorithm showed great repeatability (ICC>0.91 in the 500µm radius and ICC>0.84 in the 750µm radius) for both metrics. Conclusion: This semi-automated algorithm seems to provide readings in agreement with those of manual capillary tracing in FA. Larger prospective studies are needed to confirm the utility of the algorithm in clinical practice.

Presbyopia correction with multifocal contact lenses: Evaluation of silent reading performance using eye movements analysis.

PURPOSE: Many activities of daily living rely on reading, thus is not surprising that complaints from presbyopes originate in reading difficulties rather in visual acuity. Here, the effectiveness of presbyopia correction with multifocal contact lenses (CLs) is evaluated using an eye-fixation based method of silent reading performance. ΜETHODS: Visual performance of thirty presbyopic volunteers (age: 50 ± 5 yrs) was assessed monocularly and binocularly following 15 days of wear of monthly disposable CLs (AIR OPTIX™ plus HydraGlyde™, Alcon Laboratories) with: (a) single vision (SV) lenses - uncorrected for near (b) aspheric multifocal (MF) CLs. LogMAR acuity was measured with ETDRS charts. Reading performance was evaluated using standard IReST paragraphs displayed on a screen (0.4 logMAR print size at 40 cm distance). Eye movements were monitored with an infrared eyetracker (Eye-Link II, SR Research Ltd). Data analysis included computation of reading speed, fixation duration, fixations per word and percentage of regressions. RESULTS: Average reading speed was 250 ± 68 and 235 ± 70 wpm, binocularly and monocularly, with SV CLs, improving statistically significantly to 280 ± 67 (p = 0.002) and 260 ± 59 wpm (p = 0.01), respectively, with MF CLs. Moreover, fixation duration, fixations per word and ex-Gaussian parameter of fixation duration, µ, showed a statistically significant improvement when reading with MF CLs, with fixation duration exhibiting the stronger correlation (r = 0.79, p < 0.001) with improvement in reading speed. The correlation between improvement in VA and reading speed was moderate (r = 0.46, p = 0.016), as was the correlation between VA and any eye fixation parameter. CONCLUSION: Average silent reading speed in a presbyopic population was found improved with MF compared to SV CL correction and was faster with binocular compared to monocular viewing: this was mainly due to the faster average fixation duration and the lower number of fixations. Evaluating reading performance using eye fixation analysis could offer a reliable outcome of functional vision in presbyopia correction.

Three-Year Results of Simultaneous Transepithelial Phototherapeutic Keratectomy and Conventional Photorefractive Keratectomy (Cretan Protocol Plus) Followed by Corneal Crosslinking for Keratoconus.

PURPOSE: The aim of this study was to present the 3-year outcomes after simultaneous transepithelial phototherapeutic keratectomy (t-PTK) and conventional photorefractive keratectomy (PRK) followed by corneal crosslinking (CXL) for keratoconus. METHODS: In this prospective, interventional case series, patients with progressive keratoconus underwent simultaneous t-PTK and conventional PRK followed by CXL (Cretan protocol plus). Visual, refractive, and topographic outcomes were evaluated along with endothelial cell density (ECD) preoperatively and at 1, 2, and 3 years postoperatively. RESULTS: Twenty-two patients (31 eyes) were enrolled. No intraoperative or postoperative complications were observed in any of the patients. Logarithm of the minimum angle of resolution (logMAR) mean uncorrected and mean corrected distance visual acuity improved from 0.81 ± 0.40 and 0.18 ± 0.21 preoperatively to 0.38 ± 0.33 ( P < 0.001) and 0.06 ± 0.12 ( P < 0.001) at 3-year follow-up. Mean spherical equivalent improved from -5.39 ± 3.89 diopters (D) preoperatively to -2.29 ± 2.65 D ( P < 0.001) at 3 years postoperatively. Mean corneal astigmatism reduced from -4.70 ± 2.86 D preoperatively to -3.55 ± 2.45 D ( P = 0.001) at 3 years postoperatively. No ECD alterations were observed throughout the 3-year follow-up ( P > 0.05). CONCLUSIONS: Simultaneous t-PTK and conventional PRK followed by CXL seems to be an effective and safe treatment for progressive keratoconus over 3-year follow-up.

Unexpected finding in ocular surface trauma: a large intraorbital foreign body (bullet).

Sometimes intraorbital foreign bodies lead to unexpected findings. A 16-year old boy was referred due to ocular surface trauma. A conjunctival laceration was detected at the level of the left caruncle with associated left exotropia, reduced adduction as well as a preretinal hemorrhage along the nasal periphery of the fundus. A blow-out fracture of the medial orbital wall was suspected and a CT scan of the orbits was scheduled which revealed the presence of a large intraorbital foreign body. The removal of the intraorbital foreign body (which proved to be a bullet) and precautionary laser photocoagulation along the nasal periphery of the left eye were performed. Ocular surface trauma may reveal unexpected findings, such as an intraorbital foreign body, requiring investigation by a CT scan.

Quantification of BNN27, a novel neuroprotective 17-spiroepoxy dehydroepiandrosterone derivative in the blood and retina of rodents, after single intraperitoneal administration.

BNN27 is a novel 17-spiroepoxy derivative of the neurosteroid Dehydroepiandrosterone with neuroprotective properties. The purpose of this study was the detection and quantification of BNN27 after single intraperitoneal administration, in the serum and retina of normal rodents. Forty-two C57BL/6 mice and 48 Sprague-Dawley rats were used for the quantification of BNN27 in the blood serum and retina, respectively. BNN27 was injected intraperitoneally (i.p.) at concentrations of 100 and 30 mg/kg of body weight (b.w.), respectively. The blood was collected with retro-orbital bleeding and the retina was isolated after enucleation at various time points. The molecule concentrations were measured with Liquid chromatography-mass spectrometry (LC-MS). Non-compartmental analysis was used to determine pharmacokinetic parameters. BNN27 was found to have an elimination constant kel  = 0.465 h-1 and mean residence time (MRT) 2.154 h in the mouse serum. The maximum concentration (Cmax ) in the retina was detected at 2 h ( tCmax ) after intraperitoneal administration and was equal to 1100 ng/g. BNN27 is rapidly eliminated from both blood and retina. In the retina specifically, it is undetectable 6 h after injection. BNN27 shows a rapid systemic elimination as anticipated by its small size and lipophilicity. It is measurable in small peripheral tissues such as the rat retina, after one single i.p. injection, using a simple method such as LC-MS. Its detection in the retina corroborates the existing biological data that the molecule crosses the blood-retinal barrier, highlighting it as a potential neuroprotective agent for retinal disease.

MRI and dual-energy CT fusion anatomic imaging in Ru-106 ophthalmic brachytherapy.

PURPOSE: Brachytherapy with Ru-106 is widely used for the treatment of intraocular tumors, and its efficacy depends on the accuracy of radioactive plaque placement. Ru-106 plaques are MRI incompatible and create severe metal artifacts on conventional CT scans. Dual-energy CT scans (DECT) may be used to suppress such artifacts. This study examines the possibility of creating fusion images from MRI scans (preoperatively) and DECT scans (with the plaque in place) as a tool for confirming the anatomic accuracy of plaque placement. METHODS AND MATERIALS: Six patients with intraocular lesions (5 with choroidal melanoma and 1 with a retinal vasoproliferative lesion) were included. Fusion images of preoperative MRI scans and DECT scans with the plaque in place were created with the Demo version of the ImFusion suite (ImFusion GmbH, Munchen Germany). Clearance margins between the tumor and plaque edge in axial, transverse, and coronal planes as well as the elevation of the posterior plaque edge from the sclera were recorded and associated with the location of the lesion. RESULTS: Plaque-tumor clearance margins for transverse, sagittal, and coronal planes were higher for anteriorly located lesions (5.13 mm ± 0.11 [5.0-5.2], 5.10 mm ± 0.26 [4.9-5.4], and 5.33 mm ± 0.45 [4.9-5.8] respectively) than for posteriorly located lesions (4.16 mm ± 1.44 [2.5-5.1], 4.13 mm ± 1.42 [2.5-5.1], and 4.2 mm ± 1.21 [2.8-5.0], respectively). The elevation of the posterior plaque edge from the sclera was 0.33 mm ± 0.28 [0-0.5] and 0.63 mm ± 0.60 [0.7-1.2] for posterior and anterior lesions, respectively. CONCLUSIONS: Fusion images between DECT and MRI scans may be used as a tool to confirm the accuracy of Ru-106 plaque placement in relation with the intraocular tumors in ophthalmic brachytherapy.

Real-time ultrasound elastographic imaging of ocular and periocular tissues: a feasibility study.

BACKGROUND AND OBJECTIVE: This study examines the value of ultrasound elastography for the examination of ocular and periocular structures. SUBJECTS AND METHODS: Five patients, aged 22 to 75 years, who each had one blind eye were included. Patients underwent ultrasound elastography of their blind eye and periocular tissues using a 7-13 MHz probe. Strain grayscale and color-coded elastographic maps were recorded. In the former, a quantitative assessment of signal intensity (corresponding to elastic properties) for specific anatomical structures was performed. RESULTS: Anterior vitreous displayed intermediate elasticity, whereas posterior vitreous displayed low elasticity. Medial and lateral rectus muscle elasticity was higher in primary position than in adduction or abduction. CONCLUSION: The pattern of elastic imaging in the vitreous cavity could be attributed to posterior vitreous detachment, whereas that of medial and lateral rectus muscles may be related to the level of muscle fiber strain.