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New methods to evaluate the effect of conventional and modified crosslinking treatment for keratoconus
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Today corneal crosslinking with ultraviolet-A photoactivation of riboflavin is an established method to halt the progression of keratoconus. In some cases, when the refractive errors are large and the visual acuity is low, conventional corneal crosslinking may not be sufficient. In these cases it would be desirable with a treatment that both halts the progression and also reduces the refractive errors and improves the quality of vision.

Aims:  The aims of this thesis were to determine whether mechanical compression of the cornea during corneal crosslinking for keratoconus using a sutured rigid contact lens could improve the optical and visual outcomes of the treatment, and also to find methods to evaluate the effect of different corneal crosslinking treatment regimens.

Methods: In a prospective, open, randomized case-control study, 60 eyes of 43 patients with progressive keratoconus, aged 18-28 years, planned for routine corneal crosslinking, and a corresponding age- and sex-matched control group was included. The patients were randomized to conventional corneal crosslinking (CXL; n=30) or corneal crosslinking with mechanical compression of the cornea during the treatment (CRXL; n=30).

Biomicroscopy, autorefractometry, best spectacle corrected visual acuity, axial length measurement, Pentacam® HR Scheimpflug photography, pachymetry, intraocular pressure measurements and corneal biomechanical assessments were performed before treatment (baseline) and at 1 month and 6 months after the treatment.

One of the articles evaluated and compared the optical and visual outcomes between CXL and CRXL, while the other three articles focused on methods to evaluate treatment effects. In Paper I, the corneal light scattering was manually quantified from Scheimpflug images throughout the corneal thickness at 8 measurements points, 0.0 to 3.0 mm from the corneal centre, in patients treated with CXL. In Paper IV the corneal densitometry (light scattering) was measured with the Pentacam® HR software, in 4 circular zones around the corneal apex and at 3 different depths of the corneal stroma, in both CXL and CRXL treated corneas. Paper III quantified the biomechanical effects of CXL in vivo.

Results: Corneal light scattering after CXL showed distinctive spatial and temporal profiles and Applanation Resonance Tonometry (ART) -technology demonstrated an increased corneal hysteresis 1 and 6 months after CXL. When comparing the refractive and structural results after CXL and CRXL, CRXL failed to flatten the cornea, and the treatment did not show any benefits to conventional CXL treatment, some variables even indicated an inferior effect. Accordingly, the increase in corneal densitometry was also less pronounced after CRXL.

Conclusions: Analysis of corneal light scattering/densitometry shows tissue changes at the expected treatment location, and may be a relevant variable in evaluating the crosslinking effect. ART -technology is an in vivo method with the potential to assess the increased corneal hysteresis after CXL treatment. By refining the method, ARTmay become a useful tool in the future. Unfortunately, CRXL does not improve the optical and visual outcomes after corneal crosslinking. Possibly, stronger crosslinking would be necessary to stabilize the cornea in a flattened position.

Place, publisher, year, edition, pages
Umeå: Umeå universitet , 2015. , p. 57
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1746
Keywords [en]
Keratoconus, crosslinking, light scattering, densitometry, keratometry, hysteresis, intraocular pressure
National Category
Ophthalmology
Research subject
Ophtalmology
Identifiers
URN: urn:nbn:se:umu:diva-110531ISBN: 978-91-7601-336-6 (print)OAI: oai:DiVA.org:umu-110531DiVA, id: diva2:862560
Public defence
2015-11-20, Hörsal 914, Unod B 9, Norrlands universitetssjukhus, Umeå, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2015-10-30 Created: 2015-10-22 Last updated: 2018-06-07Bibliographically approved
List of papers
1. Spatial distribution of corneal light scattering after corneal collagen crosslinking
Open this publication in new window or tab >>Spatial distribution of corneal light scattering after corneal collagen crosslinking
2011 (English)In: Journal of cataract and refractive surgery, ISSN 0886-3350, E-ISSN 1873-4502, Vol. 37, no 11, p. 1939-1944Article in journal (Refereed) Published
Abstract [en]

Purpose: To assess the spatial distribution and time course of increased corneal light scattering after corneal collagen crosslinking (CXL) with riboflavin and ultraviolet-A irradiation.

Setting: Umeå University Hospital Eye Clinic, Umeå, Sweden.

Design: Case series.

Methods: Eyes with keratoconus were examined with Scheimpflug photography before and 1 and 6 months after CXL. Corneal light scattering was quantified throughout the corneal thickness at 8 measurement points 0.0 to 3.0 mm from the central cornea.

Results: The study comprised 11 eyes of 11 patients. Central corneal light scattering increased significantly 1 month after CXL (P<.001). At 6 months, it decreased (P=.002); however, it was still higher than pretreatment values (P<.001). Light scattering at 1 month was more pronounced in the superficialstroma, gradually diminishing to zero at 240 μm depth. It was greater at the corneal center than 1.0 to 3.0 mm from the center. At 6 months, a second peak of light scattering occurred between 240 μm and 340 μm depth. No increased light scattering deeper than 340 μm was seen at either time point.

Conclusions: Corneal light scattering after CXL showed distinctive spatial and temporal profiles. Analysis of corneal light scattering may give an impression of tissue changes, the depth of the CXL treatment effect, and the corneal response to the treatment. Scheimpflug photography appears to be useful for this purpose.

Place, publisher, year, edition, pages
Fairfax,Va.: American Society of Cataract and Refractive Surgery, 2011
National Category
Ophthalmology
Identifiers
urn:nbn:se:umu:diva-50416 (URN)10.1016/j.jcrs.2011.05.028 (DOI)000296678400005 ()2-s2.0-80054802450 (Scopus ID)
Conference
ASCRS Symposium on Cataract, IOL and Refractive Surgery, San Diego, CA, MAR, 2011
Available from: 2011-12-13 Created: 2011-12-08 Last updated: 2023-03-23Bibliographically approved
2. Initial results from mechanical compression of the cornea during crosslinking for keratoconus
Open this publication in new window or tab >>Initial results from mechanical compression of the cornea during crosslinking for keratoconus
2014 (English)In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 92, no 7, p. 644-649Article in journal (Refereed) Published
Abstract [en]

Purpose: To compare refractive changes after corneal crosslinking with and without mechanical compression of the cornea.

Methods: In a prospective, open, randomized case-control study conducted at the Department of Ophthalmology, Umeå University Hospital, Sweden, sixty eyes of 43 patients with progressive keratoconus aged 18-28 years planned for corneal crosslinking and corresponding age- and sex-matched control subjects were included. The patients were randomized to conventional corneal crosslinking (CXL; n = 30) or corneal crosslinking with mechanical compression using a flat rigid contact lens sutured to the cornea during treatment (CRXL; n = 30). Subjective refraction and ETDRS best spectacle-corrected visual acuity (BSCVA), axial length measurement, keratometry and pachymetry were performed before and 1 and 6 months after treatment.

Results: The keratoconus patients had poorer BSCVA, higher refractive astigmatism and higher keratometry readings than the control subjects at baseline (p < 0.01). In the CXL group, BSCVA increased from 0.19 ± 0.26 to 0.14 ± 0.18 logMar (p = 0.03), and the spherical equivalent improved from -1.9 ± 2.8 D to -1.4 ± 2.4 D (p = 0.03). Maximum keratometry readings decreased after CXL from 53.1 ± 4.9 D to 52.6 ± 5.2 D (p = 0.02), and the axial length decreased in the CXL group, likely due to post-treatment corneal thinning (p = 0.03). In the CRXL group, all the above variables were unaltered (p > 0.05).

Conclusion: At 6 months, the refractive results from CRXL did not surpass those of conventional CXL treatment. Rather, some variables indicated a slightly inferior effect. Possibly, stronger crosslinking would be necessary to stabilize the cornea in the flattened configuration achieved by the rigid contact lens.

Place, publisher, year, edition, pages
John Wiley & Sons, 2014
Keywords
cornea, corneal crosslinking, keratoconus, refractive errors
National Category
Ophthalmology
Identifiers
urn:nbn:se:umu:diva-97010 (URN)10.1111/aos.12380 (DOI)000344162700028 ()24628999 (PubMedID)2-s2.0-84927169933 (Scopus ID)
Available from: 2014-12-08 Created: 2014-12-08 Last updated: 2023-03-23Bibliographically approved
3. Increased corneal hysteresis after corneal collagen crosslinking: a study based on applanation resonance technology
Open this publication in new window or tab >>Increased corneal hysteresis after corneal collagen crosslinking: a study based on applanation resonance technology
2014 (English)In: JAMA ophthalmology, ISSN 2168-6165, E-ISSN 2168-6173, Vol. 132, no 12, p. 1426-1432Article in journal (Refereed) Published
Abstract [en]

Importance: A reliable tool for quantification of the biomechanical status of the cornea in conjunction with corneal collagen crosslinking (CXL) treatment is needed.

Objective: To quantify the biomechanical effects of CXL in vivo.

Design, Setting, and Participants: A prospective, open, case-control study was conducted at the Department of Ophthalmology, Umeå University, Umeå, Sweden. Participants included 28 patients (29 eyes) aged 18 to 28 years with progressive keratoconus and corresponding age- and sex-matched healthy individuals serving as controls. All participants were monitored during a 6-month period between October 13, 2009, and November 5, 2012.

Main Outcomes and Measures: Corneal hysteresis after CXL for keratoconus.

Results: A difference in corneal hysteresis between the control group and the patients with keratoconus was found at baseline, both with an applanation resonance tonometer (ART) and an ocular response analyzer (ORA), at mean (SD) values of -1.09 (1.92) mm Hg (99% CI, -2.26 to 0.07; P = .01) and -2.67 (2.55) mm Hg (99% CI, -4.05 to -1.32; P < .001), respectively. Increased corneal hysteresis was demonstrated with an ART 1 and 6 months after CXL, at 1.2 (2.4) mm Hg (99% CI,-0.1 to 2.5; P = .02) and 1.1 (2.7) mm Hg (99% CI, -0.3 to 2.6; P = .04), respectively, but not with ORA. A decrease in corneal thickness was seen 1 and 6 months after treatment (-24 [26] µm, P < .001; and -11 [21] µm, P = .01, respectively), and a corneal flattening of -0.6 (0.7) diopters was seen at 6 months (P < .001). No significant change in intraocular pressure was identified in patients with keratoconus with any method, except for an increase at 1 month with Goldmann applanation tonometry (P = .005).

Conclusions and Relevance: To our knowledge ART is the first in vivo method able to assess the increased corneal hysteresis after CXL treatment. Given the large-scale use of CXL in modern keratoconus treatment, a tool with this capacity has a great potential value. Refinement of the ART method of measuring and quantifying corneal biomechanical properties will be a subject of further studies.

Place, publisher, year, edition, pages
American Medical Association, 2014
National Category
Ophthalmology
Identifiers
urn:nbn:se:umu:diva-97009 (URN)10.1001/jamaophthalmol.2014.3029 (DOI)000346176400008 ()25171564 (PubMedID)2-s2.0-84918496232 (Scopus ID)
Available from: 2014-12-08 Created: 2014-12-08 Last updated: 2023-03-24Bibliographically approved
4. Treatment Effect and Corneal Light Scattering With 2 Corneal Cross-linking Protocols: A Randomized Clinical Trial
Open this publication in new window or tab >>Treatment Effect and Corneal Light Scattering With 2 Corneal Cross-linking Protocols: A Randomized Clinical Trial
2015 (English)In: JAMA ophthalmology, ISSN 2168-6165, E-ISSN 2168-6173, Vol. 133, no 11, p. 1254-1260Article in journal (Refereed) Published
Abstract [en]

Importance: We describe and evaluate a complementary method to indirectly quantify the treatment effect of corneal cross-linking (CXL). Additional methods to indirectly quantify the treatment effect of CXL are needed.

Objective: To assess the spatial distribution and the time course of the increased corneal densitometry (corneal light backscatter) seen after CXL with riboflavin and UV-A irradiation.

Design, Setting, and Participants: Open-label randomized clinical trial of 43 patients (60 eyes) who were 18 to 28 years of age and had progressive keratoconus and a plan to be treated with CXL at Umeå University Hospital, Umeå, Sweden. The patients were randomized to receive conventional CXL (n = 30) using the Dresden protocol or CXL with mechanical compression of the cornea using a flat rigid contact lens sutured to the cornea during the treatment (CRXL) (n = 30). All participants were followed up during a 6-month period from October 13, 2009, through May 31, 2012.

Interventions: Corneal cross-linking according to the Dresden protocol or CRXL.

Main Outcomes and Measures: Change in corneal densitometry after CXL and CRXL for keratoconus.

Results: Of the original 60 eyes included, 4 had incomplete data. A densitometry increase was seen after both treatments that was deeper and more pronounced in the CXL group (difference between the groups at 1 month in the center layer, zone 0-2 mm, 5.02 grayscale units [GSU], 95% CI, 2.92-7.12 GSU; P < .001). This increase diminished with time but was still noticeable at 6 months (difference between the groups at 6 months in the center layer, zone 0-2 mm, 3.47 GSU; 95% CI, 1.72-5.23 GSU; P < .001) and was proportional to the reduction in corneal steepness (R = -0.45 and -0.56 for CXL and CRXL, respectively).

Conclusions and Relevance: The degree of corneal light backscatter relates to the reduction in corneal steepness after cross-linking and may become a relevant complement to other methods in evaluating the cross-linking effect, for example, when comparing different treatment regimens.

Trial Registration: clinicaltrials.gov Identifier: NCT02425150.

National Category
Ophthalmology
Identifiers
urn:nbn:se:umu:diva-110530 (URN)10.1001/jamaophthalmol.2015.2852 (DOI)000365034000008 ()26312777 (PubMedID)2-s2.0-84947442591 (Scopus ID)
Available from: 2015-10-22 Created: 2015-10-22 Last updated: 2023-03-24Bibliographically approved

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