Brahma, Arun

Jinabhai, Amit

O'Donnell, Clare

Radhakrishnan, Hema

Simo-Mannion, Luisa

Tromans, Cindy

English

The University of Manchester - Institutional Repository

The University of Manchester ResearchStructural and Optical Changes in KeratoconusDocument VersionFinal published versionLink to publication record in Manchester Research ExplorerCitation for published version (APA):O'Donnell, C., Jinabhai, A., Radhakrishnan, H., Simo-Mannion, L., Tromans, C., & Brahma, A. (2014). Structuraland Optical Changes in Keratoconus. Paper presented at The Manchester Royal Eye Hospital BicentenaryConference 2014, Manchester, United Kingdom.Citing this paperPlease note that where the full-text provided on Manchester Research Explorer is the Author Accepted Manuscriptor Proof version this may differ from the final Published version. 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Jun. 2022Structural & Optical Changes in Keratoconus Clare O'Donnell   Amit Jinabhai, Hema Radhakrishnan,  Luisa Simo-Mannion, Cindy Tromans, Arun Brahma   The University of Manchester, Manchester Royal Eye Hospital   Corneal nerves – Histological studies of KC corneas revealed abnormalities • In nerve architecture, especially at the cone apex  – e.g. thickening, tortuosity, loss of radial orientation (Al-Aqaba 2011) • But tend to report only on advanced KC and subject to artefacts – In vivo CM studies have also shown alterations to NFs in KC • Unclear at what stage these changes occur or how they relate to reported changes in corneal sensitivity Aim To investigate corneal nerve structure and sensitivity in keratoconus  Luisa Simo-Mannion3, Cindy Tromans4 Methods – 44 KC and 44 control subjects recruited • 8 mild (k≤45D), 26 moderate (45<k≤52D), 10 severe (k>52D) • Mean age 32  9 years (both groups) • Also matched for gender, iris colour, mode of correction –  Morphology of stromal and sub-basal nerves • ConfoScan 3 confocal microscope, image analysis software – Density (length fibres/total area) and thickness (mean of 10) – Corneal sensitivity assessed using Cochet-Bonnet • Centrally and at 4 peripheral locations (1mm from limbus) Stromal nerves    KC   CTRL  p-value  Density (µm/mm2 )    429.5  108.0   390.4  100.4   0.106  Thickness (µm)   8.62  4.53  5.25  1.92  0.009* Two sample t-test * Statistically significant difference Sub-basal nerves    KC    CTRL    p-value  Density (µm/mm2 )  1094.9  459.6  1846.2  527.5  <0.001*  Thickness (µm)  1.77  0.06  1.82  0.05  0.29 Two sample t-test * Statistically significant difference • NF density decreased as cornea steepened (R2=0.2, p=0.006)  Corneal sensitivity  Central  Superior  Inferior  Nasal  Temp KC (g/mm2)  1.11±0.05  1.50±0.16  1.06±0.02  1.02±0.07  1.02±0.11 CTRL (g/mm2)  1.01±0.33  1.31±0.07  1.11±0.05  1.04±0.16  1.04±0.02  p-value  0.005*  0.976  0.582  0.942  0.652 * Statistically significant difference • Significant reduction in KC at central location only  • Sensitivity reduced as cornea steepened (Rs=0.44, p=0.003)   MWUT Discussion • Confirm alterations to architecture and function – Thickening of stromal NFs seems to occur early  – Reduced sub-basal nerve density and reduced sensitivity more apparent as disease progresses  (Bron 1984; Kinoshita et al., 1999)  KC  CTRL Discussion • Possible causes of stromal nerve thickening – Over-expression of nerve growth factor/proliferation Schwaan cells • Accumulation of secreted substances due to altered metabolism • Unclear if NF alterations causative or secondary – Refinement of in vivo techniques should improve understanding of nerve morphology  Patel and McGhee (2006) Normal  (schematic)  Keratoconus Especially with full-field image capture and analysis Corneal thinning • Aetiology of KC not fully understood, caused by stretching or by loss of tissue? – Is protrusion secondary to stromal thinning? – Or does reduced strength result in thinning and protrusion • Loss of tissue might be detected by analysing corneal volume in KC corneas – Advances in technology enable assessment of volume in-vivo Visual performance with aberration controlling soft contact lenses in keratoconus Introduction • Irregular corneas in keratoconus lead large magnitudes of irregular astigmatism and ocular aberrations (particularly vertical coma).  • RGP contact lenses mask most of the induced anterior corneal surface aberrations. Introduction • Soft contact lenses offer certain advantages over RGPs and can mask irregular corneal astigmatism to a limited extent.     • Technology available to make customised aberration-controlling soft contact lenses (ACCLs) to reduce ocular aberrations in keratoconic patients.   Aim • To investigate how toric soft CLs and customised ACCLs alter higher order aberrations and visual performance in keratoconus compared to patient’s habitual correction.  • Customised ACCLs were designed either to fully (100%) or partially (50%) correct the third order coma aberrations.  Methods • 22 keratoconic participants took part in the study – 14 moderate, 7 severe, 1 mild KC • Data collected from one eye for each patient. • 16 participants were habitual RGP wearers and 6 were spectacle wearers. • Mean age 34 years (range 19-55 yrs).  • High contrast (95%) and low contrast (15%) visual acuities were measured with Bailey-Lovie logMAR charts. • Ocular aberrations were measured with a Shack-Hartmann aberrometer (IRX3, Imagine Eyes, Paris) Methods  Results Patient ref. Flat  K (D) Steep  K (D) Central corneal thickness (microns) CLEK severity grade Vogt's striae Apical scarring RGP lens fitting grade 1 49.8 56.0 455 Severe Present Absent DAT 2 45.6 50.0 451 Moderate Absent Absent AT 3 42.8 45.1 440 Moderate Absent Absent AT 4 45.6 48.4 434 Moderate Absent Absent AC 5 58.2 61.8 324 Severe Present Present AT 6 45.6 47.3 505 Moderate Absent Absent AT 7 47.8 52.0 419 Moderate Present Present DAT 8 52.2 55.9 503 Severe Present Present DAT 9 44.2 48.0 453 Moderate Present Absent DAT 10 44.1 49.2 461 Moderate Absent Absent DAT 11 43.9 49.4 386 Moderate Present Present DAT 12 48.6 51.9 415 Moderate Present Present DAT 13 43.4 47.3 484 Moderate Present Absent AT 14 51.4 56.4 416 Severe Present Present DAT 15 49.1 52.9 435 Severe Present Present DAT 16 47.7 53.2 420 Severe Present Absent DAT 17 43.9 46.9 422 Moderate Present Absent - 18 50.7 53.0 494 Severe Present Present - 19 44.9 48.0 477 Moderate Absent Absent - 20 43.2 46.7 462 Moderate Present Absent - 21 45.7 49.3 432 Moderate Absent Absent - 22 42.7 43.4 514 Mild Absent Absent - Results   • Compared to when uncorrected and compared to all three soft study lenses, RGP lenses significantly reduced 2nd-order cylinder RMS.  • Compared to when uncorrected, there was significantly lower coma RMS with RGP lenses (p=0.001), 100% lenses (p=0.001) and 50% lenses (p=0.0002).  Results  Results   Results Changes in aberration with accommodation Summary and discussion • As expected, RGP lenses provided better visual performances than conventional toric SCLs for keratoconic patients.   • RGP lenses on eye also showed some residual aberrations, which are likely to be due to topographical alterations at the posterior corneal surface. Summary and discussion • The 100% lenses, on average, overcorrected vertical coma, resulting in positive residual aberration.   • The 50% lenses, on average, provided either negative residual vertical coma aberration (contact lens group) or values close to zero (spectacle group).   • Wavefront sensor errors occur through overlapping spot images, spot image crossover or missing spots and scatter.   • With customised ACCLs, superfluous wavefront aberrations can become induced through small lens translations and rotations upon blinking.    Discussion  • LCVA scores measured with toric SCLs or the 50% AC lenses were best for low levels of spherical aberration (of around zero).   • Visual neural system may compensate for long-term exposure to an asymmetrically blurred retinal image in keratoconic patients.  • Customised lenses should be made with bespoke optic zone diameters to match with the pupil size of the patient.   Conclusions • The two customised ACCLs reduced uncorrected coma RMS and HORMS error in both groups.   • The patient’s habitual RGP lenses gave better visual performances than with either ACCL in the contact lens group.  • Limiting factors  – Repeatability and accuracy of aberration measurements – Lens stability  Recent collaborations  • Corneal collagen cross-linking – In-vivo and in-vitro Manchester Corneal Collagen Cross-Linking Group Dr Ithar Beshtawi:  Today 16.00 Cornea II Session Acknowledgements Collaborators • Dr Hema Radhakrishnan, Dr Luisa Simo-Mannion • Dr Amit Jinabhai, Dr Cindy Tromans,  • Mr Arun Brahma, Prof WN Charman  Funding • Vision Centre  • College of Optometrists • Central Manchester Hospitals Foundation Trust • UMIP Aim  To investigate the effect of RGP CL lens fit on ocular HOA and VA in keratcoconus Method • 25 year old KC patient – Bilateral, moderate • RE systematically fitted with RGP CLs – BOZR of 7.40 mm to 8.10 mm, in 0.10 mm steps – Menicon-EX, same diameter •  VA with over refraction recorded – LogMAR • IRX-3 HOA – 5mm pupil, up to 6th Zernike order BOZR  = 7.40  VA 0.58  STEEP HORMS = +0.35 3rd-order RMS = +0.34 Vertical coma = +0.34  No contact lens in place  VA 0.04 HORMS = +1.70 3rd-order RMS = +1.65 Vertical coma = -1.49 Wavefront aberration  map Slit-lamp appearance RGP lens specification (in mm) Wavefront aberrations (µm) HORMS = +0.23 3rd-order RMS = +0.23 Vertical coma = +0.21 BOZR  = 8.10  VA -0.30  FLAT HORMS vs. BOZR (R2 = 0.86, p = 0.005)0.200.250.300.350.407.3 7.4 7.5 7.6 7.7 7.8 7.9 8.0 8.1 8.2BOZR (mm)HORMS error (microns)Discussion • As BOZR flattened from 7.4 to 8.1mm – HORMS reduced +0.34 µm to +0.23 µm  – and VA improved +0.58 to -0.30 log units  • Flatter fits improved visual performance – Explain why patients may prefer older lenses  • Flattening and moulding effect improving profile – Disadvantages physiologically of this approach • Staining and scarring  SCL in KC • If RGP lens intolerant may refit to SCL – Expect compromise in VA • But if we could correct HOA – Visual performance may improve with SCL • Technology to manufacture lenses exists – Customised A-C soft lenses are available • What happens when KC refitted from RGPs?  – Is wash-out period necessary? Aim  To assess the changes in VA, HOA and refraction after suspending RGP CLW for one week in KC patients Methods • 16 subjects moderate/severe KC – Suspended RGP CLW • Pentacam – Ks and CCT • IRX-3 • Subjective refraction • LogMAR VA • Performed at two visits, 7 days apart after RGP lens removal Results • Reductions in VA – High (p=0.001) and low contrast (p=0.005) • Increase in ocular aberrations  – HORMS (p=0.003) • Corneal steepening (p=0.02) • Reduction in CCT (p=0.01)   Conclusion • Changes in the optical and structure –  After suspend RGP lens wear • Stabilisation time will depend on factors – Lens fit, duration of wear, topography • Important to consider – When prescribing AC-SCL Dr Hema Radhakrishnan 

Structural and Optical Changes in Keratoconus

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Structural and Optical Changes in Keratoconus

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