Search

Optical coherence tomography angiography (OCTA) is a well-established non-invasive retinal vascular imaging technique. It has been recently adapted to image the anterior segment and has shown good potential to image corneal vascularisation. The purpose of the study is to evaluate the usefulness of OCTA to monitor regression of corneal vessels following anti-VEGF (vascular endothelial growth factor) treatment using a previously established corneal vascularisation rabbit model. The regression of vessels following the treatment with aflibercept and ranibizumab anti-VEGFs using both topical instillation and sub-conjunctival injection was quantified using OCTA and compared with ICGA (indocyanine green angiography). Overall vessel density measurements using OCTA showed good correlation (r = 0.988, p < 0.001) with ICGA, with no significant difference between the two treatment groups (p = 0.795). It was also shown that OCTA provided good repeatability outcomes of the quantitative measurements. Using Bland-Altman plots, vessel growth density values between anti-VEGF treatments were compared to control saline group. It was observed that aflibercept provided longer lasting effect than ranibizumab. We also observed that in both drugs, the topical route of administration topical provided longer regression outcomes compared to one-time sub-conjunctival injection. Thereby, with this pilot study, it was demonstrated that OCTA is a reliable imaging technique to follow-up and monitor corneal vascularisation and its treatment quantitatively.

Corneal neovascularization (CoNV) could be treated by novel anti-angiogenic therapies, though reliable and objective imaging tools to evaluate corneal vasculature and treatment efficacy is still lacking. Optical coherence tomography angiography (OCTA) -currently designed as a retinal vascular imaging system- has been recently adapted for anterior-segment and showed good potential for successful imaging of CoNV. However, further development requires an animal model where parameters can be studied more carefully with histological comparison. Our study evaluated the OCTA in suture-induced CoNV in a rabbit model compared to indocyanine green angiography (ICGA) and slit-lamp photography (SLP). Overall vessel density measurements from OCTA showed good correlation with ICGA (0.957) and SLP (0.992). Vessels density by OCTA was higher than ICGA and SLP (mean = 20.77 ± 9.8%, 15.71 ± 6.28% and 17.55 ± 8.36%, respectively, P < 0.05). OCTA was able to depict CoNV similarly to SLP and ICGA, though it could better detect small vessels. Moreover, the depth and growth of vessels could be assessed using en-face and serial-scans. This study validated the OCTA in a rabbit model as a useful imaging tool for translational studies on CoNV. This may contribute to further studies on OCTA for anterior-segment including serial evaluation of emerging anti-angiogenic therapies.

Purpose: Secreted protein acidic and rich in cysteine (SPARC) and Hevin are structurally related matricellular proteins involved in extracellular matrix assembly. In this study, we compared the anterior chamber biometric parameters and iris collagen properties in SPARC-, Hevin- and SPARC-/Hevin-null with wild-type (WT) mice., Methods: The right eyes of 53 WT, 35 SPARC-, 56 Hevin-, and 63 SPARC-/Hevin-null mice were imaged using the RTVue-100 Fourier-domain optical coherence tomography system. The parameters measured were anterior chamber depth (ACD), trabecular-iris space area (TISA), angle opening distance (AOD), and pupil diameter. Biometric data were analyzed using analysis of covariance and adjusted for age, sex, and pupil diameter. Expression of Col1a1, Col8a1, and Col8a2 transcripts in the irises was measured by quantitative polymerase chain reaction. Collagen fibril thickness was evaluated by transmission electron microscopy., Results: Mice that were SPARC- and SPARC-/Hevin-null had 1.28- and 1.25-fold deeper ACD, 1.45- and 1.53-fold larger TISA, as well as 1.42- and 1.51-fold wider AOD than WT, respectively. These measurements were not significantly different between SPARC- and SPARC-/Hevin-null mice. The SPARC-null iris expressed lower Col1a1, but higher Col8a1 and Col8a2 transcripts compared with WT. Collagen fibrils in the SPARC- and SPARC-/Hevin-null irises were 1.5- and 1.7-fold thinner than WT, respectively. The Hevin-null iris did not differ from WT in these collagen properties., Conclusions: SPARC-null mice have deeper anterior chamber as well as wider drainage angles compared with WT. Therefore, SPARC plays a key role in influencing the spatial organization of the anterior segment, potentially via modulation of collagen properties, while Hevin is not likely to be involved.

Recent developments in optical coherence tomography (OCT) systems for the cornea have limited resolution or acquisition speed. In this study we aim to evaluate the use of a 'micro-OCT' (μOCT ~1 μm axial resolution) compared to existing imaging modalities using animal models of corneal endothelial disease. We used established cryoinjury and bullous keratopathy models in Sprague Dawley rats comparing ex vivo μOCT imaging in normal and diseased eyes to (1) histology; (2) in vivo confocal microscopy (IVCM); and (3) scanning electron microscopy (SEM). Qualitative and quantitative comparisons amongst imaging modalities were performed using mean endothelial cell circularity [(4π × Area)/Perimeter(2)] with coefficient of variation (COV). We found that μOCT imaging was able to delineate endothelial cells (with nuclei), detect inflammatory cells, and corneal layers with histology-like resolution, comparable to existing imaging modalities. The mean endothelial cell circularity score was 0.88 ± 0.03, 0.87 ± 0.04 and 0.88 ± 0.05 (P = 0.216) for the SEM, IVCM and μOCT respectively, with SEM producing homogenous endothelial cell images (COV = 0.028) compared to the IVCM (0.051) and μOCT (0.062). In summary, our preliminary study suggests that the μOCT may be useful for achieving non-contact, histology-like images of the cornea for endothelial cell evaluation, which requires further development for in vivo imaging.

Purpose: To correlate the degree of anterior chamber (AC) inflammation and corneal thickness evaluated by anterior segment optical coherence tomography (ASOCT) with corneal graft rejection status and to explore the value of ASOCT in assisting the diagnosis or prediction of graft rejection using a rat penetrating keratoplasty (PK) model., Methods: A total of 40 PKs were performed using Fisher rats (allogeneic groups) and Lewis rats (syngeneic group) as donors and Lewis rats as recipients: isograft control group (n=10), allograft untreated group (n=10), and allograft with 1% prednisolone acetate treatment group (n=20). All the grafts were evaluated for 28 days by a scoring rejection index (RI) to assess the graft opacity, edema, and neovascularization using slit lamp biomicroscopy. The AC inflammation and corneal graft thickness were assessed using ASOCT., Results: All the allogeneic control grafts and four of the 20 allogeneic steroid-treated grafts developed rejection episodes. In the allogeneic treated group, the rejected grafts had a significantly higher mean AC inflammation grade at 1 week (grade 3.25±0.49 vs. 1.83±0.36, P<0.001), significantly thicker central graft thickness at 2 weeks (455.25±42.42 μm vs. 381.247±12.51 μm, P=0.047), and a significantly higher RI at 4 weeks (7.75±0.63 vs. 4.60±0.13, P<0.001) compared to the nonrejected grafts. Eyes with ≥grade 3 AC inflammation at 1 week, or with ≥400 μm central graft thickness at 2 weeks, were significantly associated with graft rejection (odds ratio [OR], 15.15, P=0.009, and OR, 9.75, P=0.014, respectively)., Conclusions: The use of ASOCT to evaluate AC inflammation and corneal thickness aids in the early evaluation and diagnosis of graft rejection in animal models. Early increased AC inflammation was an early predictor of graft failure prior to definitive clinical evaluation., (Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.)