An attempt to optimize the outcome of penetrating keratoplasty in congenital aniridia-associated keratopathy (AAK)

Purpose To propose an optimized microsurgical and medical approach to reduce the risk of complications after penetrating keratoplasty (PKP) in patients with aniridia-associated keratopathy (AAK). Methods Retrospective observational case series of 25 PKP performed in 16 patients with AAK. Preoperative indications were endothelial decompensation and vascularized scars (68%) or graft failure (32%) due to limbal stem cell deficiency. The optimized approach included a combination of a small corneal graft size (around 7.0 mm), interrupted 10–0nylon sutures, simultaneous AMT as a patch, large bandage contact lens, temporary lateral tarsorrhaphy, postoperative autologous serum eye drops, and systemic immunosuppression. Main outcome measures included: visual acuity, transplant survival, and complications encountered during follow-up of 107 weeks on average. Results A complete modified keratoplasty scheme was used in 10 of 25 PKP (group 1), while at least one of the modifications was missing in the other 15 PKP (group 2). After 8 weeks of follow-up, the epithelium was closed in 23 eyes. Visual acuity improved in 19 eyes at 6 months of follow-up, and remained stable in six eyes. None of the eyes showed a decrease in visual acuity. At the last post-operative follow-up, this visual improvement persisted in 14 eyes and graft survival rate after 156 weeks (3 years) was 69% in group 1 versus 44% in group 2 (p = 0.39, log-rank test). Secondary corneal neovascularization (8%), scarring (4%), ulcer (4%), or graft rejection (8%) happened mostly in the second group which was missing at least one of the suggested modifications. Conclusions PKP in congenital aniridia must be considered as a high-risk keratoplasty. An optimized therapeutic approach seems to be promising in order to reduce the postoperative complication rate in these most difficult eyes

Structural changes to primary visual cortex in the congenital absence of cone input in achromatopsia

Autosomal recessive Achromatopsia (ACHM) is a rare inherited disorder associated with dysfunctional cone photoreceptors resulting in a congenital absence of cone input to visual cortex. This might lead to distinct changes in cortical architecture with a negative impact on the success of gene augmentation therapies. To investigate the status of the visual cortex in these patients, we performed a multi-centre study focusing on the cortical structure of regions that normally receive predominantly cone input. Using high-resolution T1-weighted MRI scans and surface-based morphometry, we compared cortical thickness, surface area and grey matter volume in foveal, parafoveal and paracentral representations of primary visual cortex in 15 individuals with ACHM and 42 normally sighted, healthy controls (HC). In ACHM, surface area was reduced in all tested representations, while thickening of the cortex was found highly localized to the most central representation. These results were comparable to more widespread changes in brain structure reported in congenitally blind individuals, suggesting similar developmental processes, i.e., irrespective of the underlying cause and extent of vision loss. The cortical differences we report here could limit the success of treatment of ACHM in adulthood. Interventions earlier in life when cortical structure is not different from normal would likely offer better visual outcomes for those with ACHM

Structural changes to primary visual cortex in the congenital absence of cone input in achromatopsia

Autosomal recessive Achromatopsia (ACHM) is a rare inherited disorder associated with dysfunctional cone photoreceptors resulting in a congenital absence of cone input to visual cortex. This might lead to distinct changes in cortical architecture with a negative impact on the success of gene augmentation therapies. To investigate the status of the visual cortex in these patients, we performed a multi-centre study focusing on the cortical structure of regions that normally receive predominantly cone input. Using high-resolution T1-weighted MRI scans and surface-based morphometry, we compared cortical thickness, surface area and grey matter volume in foveal, parafoveal and paracentral representations of primary visual cortex in 15 individuals with ACHM and 42 normally sighted, healthy controls (HC). In ACHM, surface area was reduced in all tested representations, while thickening of the cortex was found highly localized to the most central representation. These results were comparable to more widespread changes in brain structure reported in congenitally blind individuals, suggesting similar developmental processes, i.e., irrespective of the underlying cause and extent of vision loss. The cortical differences we report here could limit the success of treatment of ACHM in adulthood. Interventions earlier in life when cortical structure is not different from normal would likely offer better visual outcomes for those with ACHM

Structural differences across multiple visual cortical regions in the absence of cone function in congenital achromatopsia

Most individuals with congenital achromatopsia (ACHM) carry mutations that affect the retinal phototransduction pathway of cone photoreceptors, fundamental to both high acuity vision and colour perception. As the central fovea is occupied solely by cones, achromats have an absence of retinal input to the visual cortex and a small central area of blindness. Additionally, those with complete ACHM have no colour perception, and colour processing regions of the ventral cortex also lack typical chromatic signals from the cones. This study examined the cortical morphology (grey matter volume, cortical thickness and cortical surface area) of multiple visual cortical regions in ACHM (n=15) compared to normally sighted controls (n=42) to determine the cortical changes that are associated with the retinal characteristics of ACHM. Surface-based morphometry was applied to T1-weighted MRI in atlas-defined early, ventral and dorsal visual regions of interest. Reduced grey matter volume in V1, V2, V3 and V4 was found in ACHM compared to controls, driven by a reduction in cortical surface area as there was no significant reduction in cortical thickness. Cortical surface area (but not thickness) was reduced in a wide range of areas (V1, V2, V3, TO1, V4 and LO1). Reduction in early visual areas with large foveal representations (V1, V2 and V3) suggests that the lack of foveal input to the visual cortex was a major driving factor in morphological changes in ACHM. However, the significant reduction in ventral area V4 coupled with the lack of difference in dorsal areas V3a and V3b suggest that deprivation of chromatic signals to visual cortex in ACHM may also contribute to changes in cortical morphology. This research shows that the congenital lack of cone input to the visual cortex can lead to widespread structural changes across multiple visual areas