Study of stereopsis using a depth sensation detection platform equipped with computer vision technology (DALE3D) / Estudio de estereopsis mediante una plataforma de detección de sensaciones de profundidad equipada con tecnología de visión por ordenador (DALE3D)

Background and objectives: The invention described herein is a prototype based on computer vision technology that measures depth perception and is intended for the early examination of stereopsis. Materials and methods: The prototype (software and hardware) is a depth perception measurement system that consists on: (a) a screen showing stereoscopic models with a guide point that the subject must point to; (b) a camera capturing the distance between the screen and the subject's finger; and (c) a unit for recording, processing and storing the captured measurements. For test validation, the reproducibility and reliability of the platform were calculated by comparing results with standard stereoscopic tests. A demographic study of depth perception by subgroup analysis is shown. Subjective comparison of the different tests was carried out by means of a satisfaction survey. Results: We included 94 subjects, 25 children and 69 adults, with a mean age of 34.2 ± 18.9 years; 36.2 % were men and 63.8 % were women. The DALE3D platform obtained good repeatability with an interclass correlation coefficient (ICC) between 0.94 and 0.87, and coefficient of variation (CV) between 0.1 and 0.26. Threshold determining optimal and suboptimal results was calculated for Randot and DALE3D test. Spearman's correlation coefficient, between thresholds was not statistically significant (p value > 0.05). The test was considered more visually appealing and easier to use by the participants (90 % maximum score). Conclusions: The DALE3D platform is a potentially useful tool for measuring depth perception with optimal reproducibility rates. Its innovative design makes it a more intuitive tool for children than current stereoscopic tests. Nevertheless, further studies will be needed to assess whether the depth perception measured by the DALE3D platform is a sufficiently reliable parameter to assess stereopsis.(AU)

Study of stereopsis using a depth sensation detection platform equipped with computer vision technology (DALE3D).

BACKGROUND AND OBJECTIVES: The invention described herein is a prototype based on computer vision technology that measures depth perception and is intended for the early examination of stereopsis. MATERIALS AND METHODS: The prototype (software and hardware) is a depth perception measurement system that consists on: (a) a screen showing stereoscopic models with a guide point that the subject must point to; (b) a camera capturing the distance between the screen and the subject's finger; and (c) a unit for recording, processing and storing the captured measurements. For test validation, the reproducibility and reliability of the platform were calculated by comparing results with standard stereoscopic tests. A demographic study of depth perception by subgroup analysis is shown. Subjective comparison of the different tests was carried out by means of a satisfaction survey. RESULTS: We included 94 subjects, 25 children and 69 adults, with a mean age of 34.2 ± 18.9 years; 36.2 % were men and 63.8 % were women. The DALE3D platform obtained good repeatability with an interclass correlation coefficient (ICC) between 0.94 and 0.87, and coefficient of variation (CV) between 0.1 and 0.26. Threshold determining optimal and suboptimal results was calculated for Randot and DALE3D test. Spearman's correlation coefficient, between thresholds was not statistically significant (p value > 0.05). The test was considered more visually appealing and easier to use by the participants (90 % maximum score). CONCLUSIONS: The DALE3D platform is a potentially useful tool for measuring depth perception with optimal reproducibility rates. Its innovative design makes it a more intuitive tool for children than current stereoscopic tests. Nevertheless, further studies will be needed to assess whether the depth perception measured by the DALE3D platform is a sufficiently reliable parameter to assess stereopsis.

Moraxella nonliquefaciens superinfecting herpes simplex keratitis.

INTRODUCTION: Moraxella nonliquefaciens (M. nonliquefaciens) is a low pathogenicity microorganism, which rarely causes ocular infections, unless there is a predisposing factor. The main clinical manifestation of M. nonliquefaciens ocular infections is endophthalmitis and only five cases of corneal infection have been reported. This work shows an update in M. nonliquefaciens corneal infections, and the first reported case of keratitis due to M. nonliquefaciens superinfecting herpes simplex infection. CASE REPORT: A 84-year old woman with worsening of her herpes simplex keratitis, diagnosed, and treated 2 days before. The slit lamp showed deep paracentral infiltrate and hypopyon. A corneal sample was collected for culture prior to initiation of empiric antibiotic therapy with vancomycin and ceftazidime fortified, oral acyclovir, and cyclopentolate. The strain was identified as M. nonliquefaciens and topical antibiotic therapy was adjusted to ciprofloxacin and ceftazidime. After 2 weeks, the epithelial defect and the infiltrate were resolved and prednisolone was added to the regimen. As the corneal oedema and neovascularization decreased, acyclovir, and prednisolone were slowly tapered. About 4 months later, the visual outcome was 20/50 and the ophthalmic examination showed a clear cornea with a paracentral leucoma. CONCLUSION: Keratitis due to M. nonliquefaciens is rare and should be suspected in patients with local predisposing factors such as corneal damage or previous corneal infection. Prompt and appropriate combined treatment for the predisposing lesions and the keratitis may improve the prognosis and avoid a more aggressive approach.

Proptosis and a Dermal Lesion as the Presenting Sign of Lung Adenocarcinoma.

The purpose is to describe a clinical case of orbital metastases as the presentation sign of the primary tumor, and the importance of a multidisciplinary diagnosis. A 70-year-old man attended the Ophthalmology Department referring ocular pain. Mild proptosis and a dermal lesion in the neck were noticed. Biopsy of the dermal lesion and systemic work-up were compatible with lung adenocarcinoma with metastatic dissemination. After one cycle of palliative chemotherapy, patient's medical condition worsened, and he eventually died. Although rare, orbital symptoms can be the initial clinical presentation preceding the diagnosis of the primary silent lung neoplasm. Ophthalmologist has an important role in diagnoses of metastatic orbital cancer. Involvement of the multidisciplinary team is important for diagnosis and treatment.

Orbital emphysema after transcanalicular laser-assisted dacryocystorhinostomy treated with needle decompression.

Orbital emphysema is an abnormal presence of air in the orbit. It usually arises after blunt trauma or periorbital surgery. When it occurs after dacryocystorhinostomy, usually it is reported as a benign condition. We present a case of a severe orbital emphysema secondary to transcanalicular diode laser-assisted dacryocystorhinostomy. The day after the surgery, the examination revealed crepitant periorbital swelling, general restriction of extraocular motility, visual loss and intraocular pressure of more than 70 mmHg. A computed tomography showed a massive orbital emphysema. An emergency decompression, using a 25-gauge needle attached to an empty syringe lacking a plunger was performed, achieving a quick decrease of intraocular pressure and pain and swelling improvement. Then, in this case, orbital decompression by passive airflow using a needle without a plunger was an effective treatment method to resolve a serious orbital emphysema after transcanalicular laser-assisted dacryocystorhinostomy.

Transforming growth factor beta-induced p.(L558P) variant is associated with autosomal dominant lattice corneal dystrophy type IV in a large cohort of Spanish patients.

IMPORTANCE: Rare transforming growth factor beta-induced (TGFBI) gene variants are involved in autosomal dominant corneal dystrophies (CDs) with heterogeneous clinical features. BACKGROUND: The purpose of this study was to analyse TGFBI gene variants and genotype-phenotype correlations in a cohort affected by atypical stromal CD. DESIGN: Retrospective cohort study (from May 2014 to September 2017). PARTICIPANTS: Thirty-five individuals from 10 unrelated South European families presenting atypical lattice CD (LCD) were included. METHODS: Corneal phenotypes were assessed by slit-lamp examination and optical coherence tomography (OCT). Contrast sensitivity was measured under mesopic conditions. Genomic DNA was obtained from blood samples, and all 17 TGFBI exons were screened for variants by Sanger sequencing. MAIN OUTCOME MEASURES: p.(L558P) variant of TGFBI gene. RESULTS: The p.(L558P) variant was identified in 22 members of the 10 families diagnosed with atypical LCD, characterized by late-onset and absence of recurrent erosion syndrome. OCT revealed punctiform deposits in the deep-mid stroma and normal anterior stroma. This variant was demonstrated to be transmitted with the disease according to autosomal dominant inheritance in most families. CONCLUSIONS AND RELEVANCE: To the best of our knowledge, we describe a detailed clinical characterization of the largest CD cohort carrying the TGFBI p.(L558P) variant. We propose that the atypical phenotype of this recently reported alteration can be classified as a form of LCD type IV. The results show that OCT and anterior-posterior analysis of the stromal location of the opacities, along with a genetic analysis of TGFBI, are required to ensure accurate diagnosis and management of CDs.

Topical axitinib is a potent inhibitor of corneal neovascularization.

BACKGROUND: This study evaluated the effects of topically applied axitinib, a tyrosine kinase inhibitor, in an experimental model of corneal neovascularization (CNV). METHODS: A total of 48 New Zealand rabbits were used. CNV was induced by placing five silk sutures in the upper cornea of one eye per rabbit. Rabbits were randomized into four groups (12 rabbits each): 0.9% saline (control group), 0.02 mg/mL axitinib, 0.35 mg/mL axitinib and 0.5 mg/mL axitinib groups. All treatments were administered three times daily for 14 days. Photographs were taken using a slit lamp on days 7 and 14. The area of neovascularization was measured in mm2 , as the percentage of total corneal area and as the percentage of corneal surface covered by sutures (SCS). RESULTS: On day 14, the CNV area in the control group (31.50 ± 7.47 mm2 ; 115.00 ± 22.55% of the corneal SCS) was larger than that in the 0.02 mg/mL axitinib group (19.20 ± 8.92 mm2 ; 73.89 ± 34.98%), the 0.35 mg/mL axitinib group (8.83 ± 3.92 mm2 ; 31.90 ± 13.59%) and the 0.5 mg/mL axitinib group (5.12 ± 3.97 mm2 ; 18.38 ± 13.65%). Compared with saline, CNV was inhibited 39.04% by 0.02 mg/mL axitinib, 71.96% by 0.35 mg/mL axitinib and 84.73% by 0.5 mg/mL axitinib. CONCLUSION: Topical administration of the three axitinib concentrations inhibited CNV in rabbits, blocking both vascular endothelial growth factor and platelet-derived growth factor pathways. Axitinib at 0.5 mg/mL induced profound inhibition of corneal angiogenesis.

Evaluation of macular thickness changes after intracameral vancomycin in cataract surgery.

The purpose of this study was to determine the effect of intracameral injection of vancomycin at the end of routine cataract surgery on macular thickness using spectral domain optical coherence tomography. This prospective comparative case series included sixty eyes of 42 patients undergoing cataract surgery. Eyes were divided into two groups: 30 eyes (Group 1) received an intracameral injection of vancomycin (1 mg/0.1 ml) at the end of surgery, and 30 eyes (Group 2) received an intracameral injection of cefuroxime (1 mg/0.1 ml). Visual acuity, average macular thickness, and retinal thickness in 9 Early Treatment Diabetic Retinopathy Study (ETDRS) sectors were measured at baseline, and 1 week, 1 month, and 3 months after surgery. There were no differences in age, gender, visual acuity, and preoperative macular thickness between groups. In Group 1, average macular thickness significantly increased 1 month after surgery compared with baseline (P = 0.000) and then stabilized. Retinal thickness significantly increased in most of the ETDRS map sectors at 1-month follow-up. In Group 2, there was a significant increase in average macular thickness 1 month after surgery compared with baseline (P = 0.037). Likewise, retinal thickness increased in most of the ETDRS subfields at 1 month. Postoperative retinal thickness values and best-corrected visual acuity were similar in both groups 1 week, 1 month, and 3 months after surgery. Intracameral injection of vancomycin at the end of cataract surgery showed comparable effects to cefuroxime in terms of macular thickness changes and visual acuity.

Corneal endothelial changes after intracameral vancomycin injection in cataract surgery.

PURPOSE: To evaluate corneal endothelial changes after intracameral injection of vancomycin at the end of routine cataract surgery. SETTING: Department of Ophthalmology, Hospital Virgen de los Lirios, Alcoy, Alicante, Spain. DESIGN: Prospective comparative case series. METHODS: Eyes received an intracameral injection of vancomycin (1 mg/0.1 mL) or cefuroxime (1 mg/0.1 mL) at the end of surgery. The visual acuity, corneal clarity, pachymetry, anterior chamber reaction, endothelial cell density (ECD), coefficient of variation (CoV), and hexagonality were evaluated at baseline and 1 week, 1 month, and 3 months after surgery. RESULTS: Sixty eyes (42 patients), 30 in each group, were enrolled. In the vancomycin group, there was a significant decrease in ECD 1 week after surgery (P = .000), after which the ECD stabilized. There were no statistically significant changes in postoperative CoV values between preoperatively and postoperatively, although there was a transient decrease in hexagonality 1 week after surgery (P = .006). In the cefuroxime group, the ECD significantly decreased 1 week after surgery (P = .000) and then stabilized. There was a statistically significantly decrease in the CoV between preoperatively and 3 months postoperatively (P = .014). No changes were noted in hexagonality. The postoperative ECD, CoV, and hexagonality values were not significantly different between the vancomycin group and the cefuroxime group. CONCLUSIONS: Endothelial cell changes observed after intracameral vancomycin were similar to those observed after intracameral cefuroxime in cataract surgery. The results indicate that intracameral vancomycin is safe for use in cataract surgery. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

New corneal neovascularization model in rabbits for angiogenesis research.

PURPOSE: To evaluate a new experimental model of suture-induced corneal neovascularization (NV) for angiogenesis research. METHODS: The new model was created in the right eye of 20 New Zealand rabbits using 5 interrupted silk sutures following an inverted triangle pattern. At different time points after suture placement, calibrated photographs were taken to quantify the corneal surface covered by the sutures (SCS) and the corneal NV response. At the end of the experiment, the corneas were processed for histological study. RESULTS: Vascular sprouts were already observed on the 3rd day. On the 7th day, the mean corneal NV surface was 19.02 ± 4.65 mm(2). On the 14th day, the mean corneal NV surface increased up to 28.96 ± 6.33 mm(2), representing 112.18% of the SCS and 21.04% of the total corneal surface. Histological sections showed that the new vessels were located at the two anterior thirds of the corneal stroma with an intense inflammatory infiltration. CONCLUSION: Our results indicate that this experimental model is effective, reliable and reproducible to induce corneal NV for angiogenesis research.

Inhibition of corneal neovascularization by topical bevacizumab (Anti-VEGF) and Sunitinib (Anti-VEGF and Anti-PDGF) in an animal model.

PURPOSE: To evaluate the effects of topically applied bevacizumab and sunitinib on experimentally induced corneal neovascularization. DESIGN: Experimental animal study. METHODS: Thirty-six New Zealand rabbits were involved. One eye per rabbit was used. Corneal neovascularization was induced by placing 5 silk sutures in the upper cornea. Rabbits were randomized to 1 of 3 groups (12 rabbits each): Group 1 received saline 0.9%, Group 2 bevacizumab 5 mg/mL, and Group 3 sunitinib 0.5 mg/mL. All treatments were administered 3 times daily for 14 days. Photographs were taken on a slit lamp on days 7 and 14, and angiographic photographs were taken on day 14. The area of neovascularization was measured in mm(2), percentage of the total corneal area, and percentage of the corneal surface covered by sutures. RESULTS: On day 14, corneal neovascularization area in Group 1 (25.92 ± 5.08 mm(2), 18.78% ± 3.5% of corneal surface, 105.59% ± 18.9% of corneal surface with sutures) was larger than in Groups 2 (18.52 ± 7.94 mm(2), 13.67% ± 5.8%, 76.35% ± 33.2%) (1-way analysis of variance, P = .041) and 3 (4.57 ± 2.32 mm(2), 3.40% ± 1.7%, 18.94% ± 9.2%)(P < .001). Neovascularization in Group 2 was larger than in Group 3 (P < .001). Compared to saline, corneal neovascularization was inhibited 28.5% by bevacizumab and 82.3% by sunitinib. Sunitinib settled on the iris. CONCLUSIONS: Topical administration of both bevacizumab and sunitinib inhibits corneal neovascularization in rabbits. But vascular endothelial growth factor (VEGF) pathway blockade by bevacizumab was not sufficient for a profound inhibition. Blocking both VEGF and platelet-derived growth factor pathways using sunitinib was 3-fold more effective.

CYP1B1 mutations in Spanish patients with primary congenital glaucoma: phenotypic and functional variability.

PURPOSE: To analyze the contributions of cytochrome P4501B1 (CYP1B1) mutations to primary congenital glaucoma (PCG) in Spanish patients. METHODS: We analyzed, by polymerase chain reaction (PCR) DNA sequencing, the presence of promoter (-1 to -867) and exon CYP1B1 mutations in 38 unrelated Spanish probands affected by PCG. Functional analysis of nine identified mutations was performed measuring ethoxyresorufin O-deethylation activity and CYP1B1 stability in transiently transfected human embryonic kidney 293T (HEK-293-T) cells. RESULTS: We found a total of 16 different mutations in 13 (34.2%) index cases. The identified mutations included nine missense and three nonsense nucleotide changes, three small deletions, and a short duplication. Eleven probands were compound heterozygotes and two were heterozygotes. Six of the identified mutations were novel (A106D, E173X, F261L, E262X, W341X, and P513_K514del). Mutations T404fsX30 and R355fsX69 were the most prevalent among index cases and were detected in six (23.0%) and three (11.5%) patients, respectively. Functional analysis showed that the three nonsense mutants assayed (E173X, E262X, and W341X) and F261L were null alleles. Of the remaining mutants, four (P52L, G61E, Y81N, and E229K) showed catalytic activities ranging from 20% to 40% of wild-type CYP1B1 and high protein instability. Mutation P400S showed normal catalytic activity and moderate instability. These five mutants were classified as hypomorphic alleles. Patients carrying two null alleles showed severe phenotypes featured by very early PCG onset usually at birth or in the first month of life (0.6+/-0.9 months). Incomplete penetrance was detected in patients carrying hypomorphic alleles. CONCLUSIONS: Our data indicate that approximately one-third of Spanish patients with PCG carry loss-of-function CYP1B1 and show that null alleles are associated with the most severe phenotypes. Hypomorphic alleles may contribute to some cases of incomplete penetrance.

MYOC gene mutations in Spanish patients with autosomal dominant primary open-angle glaucoma: a founder effect in southeast Spain.

PURPOSE: Primary open angle glaucoma (POAG) is a genetically heterogeneous disease resulting in optic disc cupping and visual impairment. It can be inherited as either a complex or a monogenic trait. Autosomal dominant POAG is the most frequent type of monogenic glaucoma. In this study, we investigated the role of myocilin MYOC in Spanish patients with autosomal dominant POAG. METHODS: We retrospectively analyzed the MYOC gene by PCR-DNA sequencing in five Southeast Spanish families and one Colombian family of Hispanic origin affected by autosomal dominant juvenile-onset open angle glaucoma (JOAG). We also analyzed two families with adult-onset POAG (AOAG). RESULTS: MYOC mutations D380A and P370L segregated with the disease in the five JOAG Spanish families and the Colombian family, respectively. Neither MYOC mutations nor cytochrome P4501B1 CYP1B1 mutations were detected in the AOAG families. The disease showed an insidious onset in D380A carriers, making early diagnosis difficult. A delay in diagnosis resulted in severe visual impairment. Topical medications were effective in controlling intraocular pressure (IOP) in D380A carriers, but 72.2% of them required surgery for long-term IOP control. Conversely, only 30% of AOAG patients required surgery. Mutation P370L was associated with a severe phenotype unresponsive to medical treatment. Analysis of the four MYOC-linked polymorphic microsatellite markers in the JOAG Spanish families revealed a common disease haplotype, indicating that the D380A mutation was inherited from the same founder. CONCLUSIONS: This is the first evidence of a founder effect for a MYOC mutation in Spanish JOAG patients. Analysis of the MYOC gene in Spanish patients with JOAG is useful to identify at-risk individuals thus help prevent visual impairment through early treatment.

Role of MYOC and OPTN sequence variations in Spanish patients with primary open-angle glaucoma.

PURPOSE: To retrospectively investigate the contribution of myocilin (MYOC) and optineurin (OPTN) sequence variations to adult-onset ocular hypertension (OHT) and primary open-angle glaucoma (POAG) in Spanish patients. METHODS: The promoter region and the three exons of MYOC were analyzed by direct PCR DNA sequencing in 40 OHT and 110 POAG unrelated patients. We used 98 subjects in whom OHT or glaucoma had been ruled out as controls. We also screened the complete coding region of the OPTN gene (exons 4-16) in all subjects by single-stranded conformational polymorphisms (SSCPs). RESULTS: We identified six common single nucleotide polymorphisms (SNPs) in the promoter region of MYOC (-1000C>G, -387C>T, -306G>A, -224T>C, -126T>C and -83G>A) and a polymorphic GT microsatellite (-339(GT)11-19). In addition, we detected four novel, rare DNA polymorphisms. None of these DNA sequence variations were associated with either OHT or POAG. We also found three (2.7%) POAG patients with MYOC pathogenic mutations. Two of these pathogenic mutations (Gln368Stop and Ala445Val) were previously described whereas the third (Tyr479His) was novel. Transient expression of the novel mutation in 293T cells supported its pathogenicity. Only two OPTN polymorphisms, which are not associated with the disease, were detected. CONCLUSIONS: Overall, our data show that in Spain a minority of adult-onset high-pressure POAG patients carry heterozygous disease-causing mutations in the MYOC gene and that OPTN is not involved in either OHT or POAG.