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.

Progression of Macular Atrophy in Patients Receiving Long-Term Anti-VEGF Therapy for Age-Related Macular Degeneration: Real-Life Data.

PURPOSE: This study aimed to evaluate the progression of macular atrophy (MA) based on near-infrared reflectance (NIR) and optical coherence tomography (OCT) images, in patients with age-related macular degeneration (AMD), receiving anti-vascular endothelial growth factor (anti-VEGF) treatment for at least a 6-year period. MATERIALS AND METHODS: This retrospective study included 53 naïve patients (53 eyes) with neovascular AMD from 2 centers, who were treated with anti-VEGF intravitreal injections and had no MA at baseline. MA was evaluated in an annual basis using NIR images, while all available OCT images were used to confirm that the atrophic area fulfilled the criteria proposed by the Classification of Atrophy Meetings (CAM) group for complete retinal pigment epithelium and outer retinal atrophy. Incidence and progression of MA were evaluated. Associations with best-corrected visual acuity (BCVA) and total number of injections were also studied. RESULTS: Treatment duration of our patients was 7.34 ± 1.54 years. The mean number of anti-VEGF injections was 24.4 ± 13.6. BCVA at baseline was 0.38 ± 0.27 logMAR, while at the final visit, it was 0.60 ± 0.35 logMAR (p = 0.731). The cumulative incidence of new MA at years 1, 2, 3, 4, 5, and 6 was 1.89%, 18.87%, 32.08%, 39.62%, 49.06%, and 50.94%, respectively. In patients who developed MA, mean MA area increased from zero at baseline to 5.66 ± 7.18 mm2 at the final visit. The estimated annual enlargement of MA was 0.45 mm/year based on square root transformation (1.12 mm2/year, untransformed data). MA progression does not appear to be significantly associated with age (R = 0.055; p = 0.784), gender (R = 0.113; p = 0.576), BCVA (R = 0.168; p = 0.404), and total number of injections (R = 0.133; p = 0.255). CONCLUSION: In this real-life setting, half of the neovascular AMD patients under anti-VEGF treatment, without MA at therapy initiation, developed MA over a period of at least 6 years. In this work, the number of injections did not seem to have a significant association with MA progression.

Association between HPV detection in swab samples and tissue specimens and ophthalmic pterygium recurrence.

PURPOSE: To investigate the presence of HPV on the ocular surface after surgical excision of HPV infected pterygia and the possible correlation of HPV with pterygium postoperative recurrence. MATERIALS AND METHODS: Both exfoliative pterygium swab samples and respective tissue specimens were received and analyzed with real-time PCR for the detection of HPV-infected pterygia. In addition, swab samples from patients that had HPV-infected pterygia with no recurrence after 1 year of follow-up, as well as swab samples from patients with healthy conjunctiva, were analyzed. RESULTS: Forty eyes with pterygium of 40 patients and 40 eyes with normal conjunctiva were included in the study. HPV virus was detected in the tissue specimens of 11 patients (27.5%) and in the swabs of 9 patients (22.5%). The HPV subtypes detected were 33, 39, 45, 56, 59, 66, and 68. The swab test had sensitivity of 81.82% and 100% specificity. In 15 (43%) patients, a bare sclera technique was used for pterygium removal and eleven of these patients showed recurrence of the disease. Surgical excision with use of autologous conjunctival graft was performed in twenty patients and five of them had recurrence. Patients with recurrent disease were 12.41 times more likely to have an HPV-infected pterygium (p = 0.031). Furthermore, from the 11 HPV positive patients, six had no recurrence, 1 year after surgery. In five of them, a swab sample was taken from the site of the surgical excision 1 year after surgery and real-time PCR was negative for HPV presence. CONCLUSION: Persistence of HPV infection seems to be correlated with postoperative pterygium recurrence. Further investigation with the use of the minimally invasive proposed swab technique may contribute in the understanding of pterygium pathogenesis and in the development of a more efficient treatment planning.

Efficacy of Topical Nepafenac 0.3% in the Management of Postoperative Cystoid Macular Edema.

PURPOSE: To assess the effect of twice-daily nepafenac ophthalmic suspension 0.3% on postoperative cystoid-macular-edema (CME). PATIENTS AND METHODS: In this prospective, clinic-based, non-randomized case-series, 21 patients (21 eyes) were enrolled with either acute or chronic postoperative CME after cataract extraction. Patients were treated with twice-daily nepafenac 0.3% drops, and followed for at least a 4-month period. Best-corrected visual acuity (BCVA) and spectral-domain optical coherence tomography (SD-OCT)-derived central retinal thickness (CRT) were measured. RESULTS: From 21 patients, eight presented with acute postoperative CME and 13 with chronic CME. Mean follow-up was 4.82±1.24 months. No adverse events were reported during the study. Baseline BCVA was 0.49±0.36 logMAR and improved to 0.36±0.42 logMAR at the last follow-up visit (P<0.005). CRT decreased from 450.40±90.74 µm at baseline to 354.60±81.49 µm (P<0.05), following treatment. CONCLUSION: Our outcomes strongly suggest that administrating nepafenac 0.3% drops on a twice-daily regimen could be a promising alternative for the management of postoperative CME. Additional studies are necessary to further validate our results.

Orbital volume measurements from magnetic resonance images using the techniques of manual planimetry and stereology.

INTRODUCTION: Current volume measurement techniques, for the orbit, are time-consuming and involve complex assessments, which prevents their routine clinical use. In this study, we evaluate the applicability and efficacy of stereology and planimetry in orbital volume measurements using magnetic resonance imaging (MRI). MATERIALS AND METHODS: Prospective imaging study using MRI. Sheep craniums and human subjects were evaluated. Water-filling measurements were performed in animal skulls, as the standard validation technique. Planimetry and stereology techniques were used in each dataset. Intraobserver and interobserver reliability testing were applied. RESULTS: In stereology customization, 1/6 systematic sampling scheme was determined as optimal with acceptable coefficient of error (3.09%) and low measurement time (1.2 min). In sheep craniums, the mean volume measured by water displacement, planimetry, and stereology was 17.81 ± 0.59 cm3, 18.53 ± 0.24 cm3, and 19.19 ± 0.17 cm3, respectively. Planimetric and stereological methods were highly correlated (r = 0.94; P ≈ 0.001). The mean difference of the orbital volume using planimetry and stereology was 0.316 ± 0.168 cm3. In human subjects, using stereology, the mean orbital volume was found to be 19.62 ± 0.2 cm3 with a CE of 3.91 ± 0.15%. CONCLUSIONS: The optimized stereological method was found superior to manual planimetry in terms of user effort and time spent. Stereology sampling of 1/6 was successfully applied in human subjects and showed strong correlation with manual planimetry. However, optimized stereological method tended to overestimate the orbital volume by about 1 cc, a considerable limitation to be taken in clinical practice.

Endogenous endophthalmitis: A case of a presumed mixed intraocular opportunistic infection by a fungal species and cytomegalovirus.

BACKGROUND: Endogenous endophthalmitis is a serious sight-threatening disease. Common causes include immunocompromised state and intravenous drug use, permitting opportunistic pathogens to reach the eye through the blood stream. We reported a rare case of a presumed simultaneous opportunistic intraocular fungal and cytomegalovirus (CMV) infection. Case presentation: A 67-year-old male patient with a recent history of hospitalization due to pneumonia, presented to our department with bilateral loss of vision. Ocular examination revealed low visual acuity, signs of vitritis with chorioretinal infiltrations and cotton ball colony-like lesions, bilaterally. A bilateral endogenous fungal endophthalmitis was suspected and topical and systemic antifungal treatment was initiated. Nevertheless, vitreous and blood cultures were negative for fungi and other bacteria, while serological examinations revealed primary infection with CMV. Following vitrectomy, polymerase chain reaction (PCR) of vitreous washings confirmed the intraocular infection with CMV. Treatment was modified, including intravenous administration of Gancyclovir. In the following days, the patient's clinical signs and visual acuity improved remarkably. Conclusions: A case of a presumed mixed fungal and CMV intraocular infection was presented. High level of suspicion with prompt diagnosis and aggressive combination treatment led to a favorable result.

Ex vivo orbital volumetry using stereology and CT imaging: A comparison with manual planimetry.

OBJECTIVES: To evaluate the applicability of stereology and planimetry in orbital volume measurements using computed tomography (CT) and to compare the results between the two measurements. METHODS: Experimental study using sheep craniums for CT imaging. Water filling measurements were performed, as the validation technique. Quantification techniques were also evaluated in five human subjects. To examine the proportion of agreement among measurements, we tested intra- and inter-observer agreement. RESULTS: For stereology customization, a 1/8 systematic sampling scheme was considered as optimal; this resulted in a low coefficient of error (2.59 %) and low measurement time (1.9 mins). In sheep craniums, mean volume measured by water displacement, planimetry and stereology was 17.81 ± 0.59 cm3, 17.87 ± 0.68 cm3 and 17.54 ± 0.49 cm3, respectively. Total volumes, obtained by stereology, were highly correlated with the water-filling method (r=0.893; p = 0.001) and a paired t-test showed significant difference between methods (t=3.047; p = 0.014). Planimetry results displayed a high correlation with the water-filling method (r=0.957; p ≈ 0.001) but no statistically significant difference was found (p = 0.154). Mean difference using planimetry and stereology was 0.332 ± 0.322 cm3. In human subjects, using stereology, the estimated volume ranged between 18.57 cm3 and 19.27 cm3, and the mean orbital volume was 19.05 ± 0.50 cm3 with CE=3.75 ± 0.16 %. Mean measure time was 2.1 ± 0.1 mins. CONCLUSIONS: Stereological measurements were superior to manual planimetry in terms of user effort and time spent. Stereology sampling of 1/8 was successfully applied in human subjects and yielded a strong correlation with manual planimetry. KEY POINTS: • Stereology can be applied to measure the orbital volume using computed tomography. • Stereological measurements display high correlation with gold standard planimetry and combine low coefficient of error (2.59%) with low measurement time (1.9 min). • Stereology is superior in terms of user effort and time spent.

Quantification of effective orbital volume and its association with axial length of the eye. A 3D-MRI study.

Objective: To measure the effective orbital volume (EOV) from magnetic resonance images, and investigate its relationship with axial length (AL) in those parameters. Methods: Cross-sectional, 3D-MRI study. 54 eyes of 54 patients (25 males) were included in this work. Patient weight, height and head circumference were also measured. Orbital and eyeball volumes were calculated after image segmentation. The difference between those values volume was assessed, estimating the EOV for each eye. Results: Mean eyeball volume was 7.83 ± 2.27 mm3, mean orbital volume 26.81 ± 0.59 mm3 and EOV 21.64 ± 0.19 mm3. The orbital volume was significantly higher in the male group (Wilcoxon signed-rank tests Z=-1.51, p<0.001; Z=-3.57, p<0.001 respectively). EOV was significantly correlated with AL in both males (r=-0.71, p<0.001) and females (r=-0.73, p<0.001), whereas it was also significantly associated with patient height (r=0.261, p=0.03). Associations between EOV and other age, axial and anthropometric characteristics were not statistically significant. Conclusions: Findings of this study could be of valuable importance in various clinical situations in which quantification of orbital volume is needed, such as orbital decompression in Graves' orbitopathy, volume restoration in orbital fractures or other orbital reconstructive surgery. In surgical interventions, clinical relationships should be carefully taken under consideration to avoid iatrogenic injury. Abbreviations: EOV = Effective orbital volume, AL = Axial length, ROI = Region of interest.

Optical Biometry Derived Axial Length Measurements Following Intravitreal Anti-Vascular Endothelial Growth Factor Treatment for Macular Edema.

PURPOSE: To evaluate axial length (AL) alterations in patients with macular disease over the course of intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment. METHODS: In this prospective, comparative study, 33 patients with macular edema underwent unilaterally intravitreal anti-VEGF therapy and were followed for two months; the contralateral eyes were considered as controls. Central retinal thickness (CRT) was measured with spectral-domain optical coherence tomography and AL with an IOL-Master optical biometer. RESULTS: CRT of the treated eyes decreased by 35.33 ± 65.59 µm (range, -222.00-67 µm), while AL increased by 0.008 ± 0.062 mm (range, -0.11-0.18 mm). CRT of the control group decreased by 9.82 ± 65.40 µm (range, -203-182 µm), and AL increased by 0.011 ± 0.129 mm (range, -0.20-0.67 mm). No significant correlation was detected between CRT and AL parameters (rhos=0.026, P=0.882). CONCLUSIONS: Anti-VEGF administration has no significant impact on optical biometry-derived AL measurements.

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.

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.

Evaluation of corneal stromal demarcation line depth following standard and a modified-accelerated collagen cross-linking protocol.

PURPOSE: To compare the corneal stromal demarcation line depth using anterior segment optical coherence tomography (AS-OCT) after corneal collagen cross-linking (CXL) using 2 different treatment protocols: the standard Dresden protocol (30 minutes with 3 mW/cm(2)) and a modified-accelerated protocol (14 minutes with 9 mW/cm(2)). DESIGN: Prospective, comparative study. METHODS: Forty-three keratoconic patients (52 eyes) were enrolled. All patients underwent CXL using the same high-intensity ultraviolet-A (UV-A) irradiation device. Twenty-six eyes were treated for 30 minutes with 3 mW/cm(2) according to the standard Dresden protocol (Group 1), while 26 eyes were treated with a novel modified-accelerated CXL protocol for 14 minutes with 9 mW/cm(2) of UV-A irradiation intensity (Group 2). One month postoperatively, corneal stromal demarcation line depth was measured by 2 independent observers using AS-OCT. RESULTS: Corneal stromal demarcation line depth was assessed with no significant difference between observer measurements for both groups (P = .676 for Group 1 and P = .566 for Group 2). Mean corneal stromal demarcation line depth was 337.00 ± 46.46 µm for Group 1 and 322.91 ± 48.28 µm for Group 2. There was no statistically significant difference (P = .243) in the corneal stromal demarcation line depth between the 2 groups. CONCLUSIONS: Corneal stromal demarcation line depth using UV-A with 3 mW/cm(2) for 30 minutes and 9 mW/cm(2) for 14 minutes was similar. A modified-accelerated protocol of 14 minutes of CXL provided the same treatment depth as the classic Dresden protocol.