Assessment of Health Disparities and Barriers to Accessing Keratoconus and Crosslinking at a Tertiary Referral Center.

PURPOSE: The aim of this study was to determine the barriers to accessing the crosslinking service in Auckland, New Zealand. METHODS: This was a prospective 1-year study of patients at Auckland District Health Board. Studied parameters included age, sex, body mass index, ethnicity, New Zealand Deprivation (NZDep; an area-based measure of socioeconomic status, 1 = low deprivation-10 = high deprivation) score of residence, disease severity (maximum keratometry and thinnest corneal thickness), attendance, distance travelled, car ownership, employment status, and visual outcomes. Statistical analysis was performed using independent t tests, Pearson correlation, independent samples ANOVA, MANCOVA, and binomial logistic regression. RESULTS: Four hundred fifty-four patients with keratoconus were analyzed and had a mean age of 24.1 ± 0.8 years, mean body mass index of 33.0 ± 9.7 kg/m 2 , and 43% were female. Pacific Peoples consisted 40.2% of the population; Maori 27.2%; Europeans 21.2%; Asian 9.9%; and Middle Eastern, Latin American, and African (MELAA) 1.3%. The mean distance travelled was 12.5 ± 9.5 km, NZDep score was 6.8 ± 2.6, and attendance was 69.0 ± 42.5%. The lowest attendance was observed in Pacific Peoples (58.9%) and the highest was in Asians (90%) ( P = 0.019). The mean worst-eye visual acuity at attendance was 0.75 ± 0.47 logMAR (6/35). Unemployment was associated with worse best-eye visual acuity at FSA ( P = 0.01) and follow-up ( P < 0.05). Maori and Pacific Peoples had the highest NZDep ( P < 0.001), were younger at presentation ( P = 0.019), had higher disease severity ( P < 0.001), and worse visual acuity ( P < 0.001). CONCLUSIONS: Poor attendance was seen in this cohort. Pacific Peoples and Maori presented younger with worse disease severity and visual acuity but also had the highest nonattendance. These results suggest that deprivation, factors associated with ethnicity, and unemployment are potential barriers to attendance.

Repeatability of Scheimpflug based corneal tomography parameters in advanced keratoconus with thin corneas.

OBJECTIVE: To determine the repeatability limits of corneal tomography parameters in patients with advanced and moderately thin keratoconic corneas to assist in planning thickness-based procedural interventions. METHODS: Prospective, single-centre, repeatability study. Three tomography scans using the Pentacam AXL were obtained from patients with keratoconus with thinnest corneal thickness (TCT) ≦400 µm (sub-400 group) and compared to those with TCT = 450-500 µm (450-plus group). Eyes with previous crosslinking, intraocular surgery, or acute corneal hydrops were excluded. Eyes were age and gender-matched. The within-subject standard deviations for flat keratometry (K1), steep keratometry (K2), maximal keratometry (Kmax), astigmatism and TCT were used to calculate respective repeatability limits (r). Intra-class correlation coefficients (ICC) were also analysed. RESULTS: The sub-400 group comprised 114 eyes from 114 participants, and the 450-plus group comprised 114 eyes from 114 participants. In the sub-400 group, TCT was amongst the least repeatable parameters (33.92 µm; ICC 0.96), compared with the 450-plus group (14.32 µm; ICC 0.99, p < 0.01). In the sub-400 group, K1 and K2 of the anterior surface were the most repeatable parameters (r 3.79 and 3.22 respectively; ICC 0.97 and 0.98 respectively) compared with the 450-plus group (r 1.17 and 0.92 respectively; and ICC 0.98 and 0.99 respectively, p < 0.01). CONCLUSIONS: The repeatability of corneal tomography measurements is significantly reduced in sub-400 keratoconic corneas when compared to 450-plus corneas. Repeatability limits should be carefully considered when surgical interventions are planned for such patients.

Rate of recurrence of toxoplasmosis retinochoroiditis at a tertiary eye centre in Auckland.

AIM: Our aim was to examine rate of recurrence of toxoplasmosis retinochoroiditis and risk factors for recurrence. No New Zealand epidemiological data on recurrence rates of toxoplasmosis retinochoroiditis have been previously published. METHODS: Retrospective chart review of all patients with toxoplasmosis retinochoroiditis presented to Auckland District Health Board Department of Ophthalmology between 2006-2019. RESULTS: One hundred and twenty-six eyes of 115 patients were included with a median age at initial diagnosis of 36.7 years (IQR 23.7-53.8). Fifty-nine patients were female (51.3%), and 16 patients (13.9%) were immunosuppressed. Twenty-six of the 86 patients tested (30.2%) were IgM positive at presentation. Mean follow-up was 6.1 years and 73 recurrences occurred during the follow-up period in 36 patients (31.3%). Treatment was initiated in 87.4% of cases, with oral cotrimoxazole or clindamycin the most common options. Recurrence occurred in 14.8% in the first year (95% CI 10.3%-21.0%), and the risk of recurrence was increased 2x for every previously documented recurrence (HR 2.00; p<0.001). There was no statistically significant increased risk of recurrence with age, IgM positivity, immunosuppression or macular involvement. CONCLUSIONS: Toxoplasmosis retinochoroiditis had a 14.8% risk of recurrence in the first year, with each previous recurrence increasing the risk by two-times.

Differences in sphere-forming cells from keratoconic and normal corneal tissue: Implications for keratoconus pathogenesis.

Keratoconus is primarily an anterior corneal disorder of unclear aetiology. Stem cells may play a role in the perpetuation of keratoconus, although this has yet to be definitively established. Sphere-forming cells from normal human donor corneas have previously been shown to be a heterogenous mix of epithelial, stromal, stem and progenitor cell components which have potential for treatment of corneal dystrophies. Our work set out to isolate and characterise sphere-forming cells from human keratoconic tissue. Keratoconic donor corneas were successfully used to culture sphere-forming cells in vitro. Time lapse imaging of these spheres on a collagen surface over 8 days revealed keratoconic spheres lack the ability to maintain a central core and have diminished ability to repopulate the surface. Immunocytochemistry showed positive labelling for the stem cell marker 'Adenosine triphosphate-binding cassette sub-family B member 5 (ABCB5)' indicating stem cell retention and the myofibroblast marker alpha smooth muscle actin indicating wound repair while droplet digital Polymerase Chain Reaction confirmed an increase in expression of stem and stromal cell markers in keratoconic spheres compared to spheres cultured from normal donors at day 7 post-placement. Keratoconic sphere-forming cells showed a diminished repopulation ability, a faster wound healing response and lack of central core retention. These results suggest stem cells in keratoconus may be in an elevated state of wound repair and unable to respond appropriately to further injury in corneal maintenance. Sphere forming cell populations in keratoconus appear to be different to those isolated from normal corneas and this may be an important consideration in unearthing keratoconus aetiology.

Sphere-forming corneal cells repopulate dystrophic keratoconic stroma: Implications for potential therapy.

BACKGROUND: Keratoconus is a degenerative corneal disease characterised by aberrant cell behaviour and loss of matrix that can result in vision loss. Cells extracted from peripheral corneas can form stem cell-enriched spheres, which have shown the potential to repopulate the normal peripheral corneal stroma in vitro upon sphere implantation but have not been previously studied in keratoconic tissue. AIM: To investigate the therapeutic potential of stem cell-enriched spheres formed from extracted peripheral human corneal cells when introduced to keratoconic tissue. METHODS: Stem cell-enriched spheres were formed from extracts of normal cadaveric human peripheral corneal cells. These spheres were implanted into incisions created in full thickness and onto the surface of 10 µm thin sections of keratoconic and normal stromal tissues in vitro. Tissue sections were used to maximise use of limited keratoconic tissue available for research. Living cells were stained with Calcein-AM and visualised with stereo and fluorescence microscopy to assess survival and behaviours between the time of implantation day 0 and 14 d (D14) from implantation. Sphere cells in implanted tissues were characterised for stem cell and differentiation markers using immunohistochemistry and droplet digital PCR to assess the potential implications of these characteristics in the use of spheres in keratoconus treatment. RESULTS: Spheres were successfully implanted into full-thickness central corneal tissue and onto the surface of 10 µm thin en face tissue sections. No observable differences were seen in sphere migration, proliferation or differentiation in keratoconic tissue compared to normal between day 0 and D14. Spheres stained positively with Calcein-AM up to D14. Cell migration increased from day 0 to D14, occurring radially in three dimensions from the sphere and in alignment with tissue edges. Cell proliferation marker, EdU, was detected at day 10. Implanted spheres stained positively for putative stem cell markers ∆Np63α and ABCB5, while ABCG2, ABCB5, ∆Np63 and p63α were detectable by droplet digital PCR up to D14. Double immunolabelling revealed absence of ABCB5 staining in migrated cells but positive staining of alpha smooth muscle actin (myofibroblast marker) in some migrated cells. Droplet digital PCR showed similar expression patterns of differentiation markers but a reduction in stem cell markers between normal and keratoconic tissue with an increase in stromal cell markers and a reduction in epithelial cell markers, indicating an appropriate response to repopulating diseased tissue. CONCLUSION: Cells from implanted stem cell-enriched spheres can repopulate a keratoconic corneal stromal surface in a directed manner and exhibit migratory stromal cell phenotypes.