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Year : 2017  |  Volume : 24  |  Issue : 3  |  Page : 121-125  

Mesopic quality of vision after accelerated 18 mW/cm2 corneal cross-linking: Mid-term results

1 Noor Ophthalmology Research Center, Noor Eye Hospital, Tehran, Iran
2 Noor Research Center for Ophthalmic Epidemiology, Noor Eye Hospital, Tehran, Iran
3 Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

Date of Web Publication9-Nov-2017

Correspondence Address:
Soheila Asgari
Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/meajo.MEAJO_244_16

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Purpose: The purpose of the study was to determine 2-year changes in mesopic higher-order aberrations (HOAs) and contrast sensitivity (CS) after accelerated corneal cross-linking (CXL) in keratoconus patients.
Materials and Methods: In this before-after interventional case series, patients with progressive keratoconus were subjected to accelerated CXL (18 mW/cm2, 5 min). Patients were examined with the OPD-Scan III and CVS-1000 grating charts under mesopic conditions at baseline and at 12 and 24 months after CXL.
Results: At 24 months after CXL, compared to baseline, mesopic CS in spatial frequencies of 3, 6, 12, and 18 cycle per degree reduced respectively to 0.09 ± 0.27, 0.09 ± 0.32, 0.11 ± 0.19, and 0.02 ± 0.10; these changes were not statistically significant (all P > 0.05). The reduction in ocular HOAs was 0.11 ± 0.43; ocular coma, trefoil, and spherical aberration (SA) decreased by 0.09 ± 0.36, 0.05 ± 0.35, and 0.00 ± 0.13 microns, respectively (all P > 0.05). Reductions in corneal HOAs (0.89 ± 7.08) including coma (0.99 ± 3.55), SA (1.14 ± 3.92), and trefoil (1.28 ± 5.53) were not statistically significant (all P > 0.05). Coma had the highest share of corneal HOAs before and 24 months after CXL and the largest 24-month decrease was seen in corneal SA.
Conclusion: At 2 years after accelerated CXL, despite reduced keratometry and corneal flattening, mesopic CS as well as ocular and corneal HOA remained unchanged, and the procedure did not cause a reduction in patients' vision quality.

Keywords: Accelerated corneal cross-linking, contrast sensitivity, higher order aberration, mesopic, visual quality

How to cite this article:
Hashemi H, Miraftab M, Asgari S. Mesopic quality of vision after accelerated 18 mW/cm2 corneal cross-linking: Mid-term results. Middle East Afr J Ophthalmol 2017;24:121-5

How to cite this URL:
Hashemi H, Miraftab M, Asgari S. Mesopic quality of vision after accelerated 18 mW/cm2 corneal cross-linking: Mid-term results. Middle East Afr J Ophthalmol [serial online] 2017 [cited 2021 Oct 22];24:121-5. Available from: http://www.meajo.org/text.asp?2017/24/3/121/217889

   Introduction Top

Collagen corneal cross-linking (CXL) is the only treatment that stops keratoconus.[1],[2] Studies have reported improved vision and refraction [3],[4] after treatment with this method. Since 2010, accelerated methods of CXL have been introduced. Various studies have demonstrated the short-and long-term effectiveness of these protocols on vision, refraction, topography, and corneal biomechanical parameters.[5],[6],[7],[8]

The impact of keratoconus on the visual quality and night vision disturbances has already been shown.[9] Since quality of vision and visual function indicate a great part of postoperative visual rehabilitation, examining postoperative changes in contrast sensitivity (CS) and aberrometry are of importance. Lamy et al.[10] have reported the improvement of photopic CS at 2 years after standard CXL. In terms of the effect of surgery on aberrations, two short-term studies have shown a lack of impact of standard CXL on higher-order aberrations (HOAs).[11],[12] Despite the importance of visual quality, to our knowledge, studies regarding the effect of CXL on CS are very limited, and there are none regarding the accelerated 18 mW/cm 2 protocol in low light condition.

Our 1-year results indicated that accelerated CXL improved mesopic CS, but mesopic HOAs unchanged. In this report, we tried to investigate the mid-term impact of accelerated CXL (18 mW/cm 2, 5 min) on CS under mesopic conditions. Since the repeatability of measurement of OPD Scan-III is desirable,[13] changes in corneal and ocular aberrations were also measured with the OPD-Scan III under mesopic conditions and are described separately.

   Materials and Methods Top

This study was performed as a before-after interventional case series on 62 patients (70 eyes). Inclusion criteria were a diagnosis of mild-to-moderate progressive keratoconus (minimum of 1 diopter [D] increase in maximum keratometry [Kmax], manifest cylinder, or spherical equivalent refraction (SE) or a loss of 2 or more lines of corrected distance visual acuity (CDVA) within 12 months before treatment) age between 15 and 35 years, Kmax<55 D, and minimum central corneal thickness of 450 μm. Hard and soft contact lens users were instructed not to wear them for 3 weeks and 3 days, respectively, before the procedure. The study adhered to the tenets of the Declaration of Helsinki at all stages and was approved by Noor Review Board. A written informed consent was obtained from the study participants.

Surgical techniques

After local anesthesia using proparacaine hydrochloride 0.5%, the central 9 mm of the corneal epithelium was manually removed. After removing the lid speculum, riboflavin drops (0.1% in 20% dextran) (Streuli Pharma, Uznach, Switzerland) were instilled onto the corneal surface every 3 min for ½ h. Before irradiation, the anterior chamber was checked at the slit lamp to ensure riboflavin saturation. Then, the cornea was exposed to a wavelength of 370 nm, 18 mW/cm 2 irradiance for 5 min from a distance of 5 cm. Irradiation was carried out using the UVX system (Peschke Meditrade GmbH, Waldshut-Tiengen, Germany). At the end of this stage, the corneal surface was rinsed with sterile balanced saline solution, a soft bandage contact lens (Night and Day, Ciba Vision, Duluth, US) was fit, and levofloxacin eye drops were instilled. Postoperative treatment included levofloxacin eye drop four times daily, and betamethasone 0.1% and preservative-free artificial tears (Hypromellose) are required. Patients were examined on days 1 and 3 after CXL, and the contact lens was removed after epithelial healing. After removing the lens, levofloxacin was discontinued, and betamethasone was continued four times daily for another week. In the absence of complete epithelial healing, visits continued daily until complete reepithelialization.

Pre- and post-corneal cross-linking examinations

Aberrometry was performed using the OPD-Scan III (Nidek, Tokyo, Japan) to measure ocular and corneal HOA including coma, trefoil, and spherical aberration (SA). To measure CS, CVS-1000 grating charts (VectorVision, Inc., OH, USA) were used. CS was measured monocularly with the best correction and physiologically dilated pupils. Tests were done without glare at a distance of 4 m.

Both tests were performed under mesopic conditions. For this purpose, daylight entry into the examination room was blocked, and room illuminance was measured and adjusted to about 15 lux. Patients were seated inside for 15 min to adjust to lighting conditions of the examination room. All examinations were performed by the same optometrist.

To determine the effectiveness of CXL along main study indices, we tested uncorrected distance visual acuity (UDVA) and CDVA using the Snellen chart and manifest refraction spherical equivalent (MRSE) using retinoscopy (ParaStop HEINE BETA 200; HEINE Optotechnik, Herrsching, Germany) as well as Kmax and minimum keratometry (Kmin) using the OPD-Scan III. The demarcation line and complications of surgery were evaluated during the slit limp (Haag-Streit, Ohio, USA) examination.

Statistical analysis

According to standard deviation (SD) = 0.9 and precision = 0.2, sample size was calculated 77, but in sampling stage, seventy cases were obtained. The trend of changes from baseline to 24 months after CXL was examined using repeated measures analysis of variance. Adjustments were made for the fellow eye correlation in bilateral cases using covariate analyses. The results are presented as mean ± SD in addition to percentages of increase and decrease in each studied index. The significance level was considered 0.05.

   Results Top

Seventy eyes of 62 patients with keratoconus were enrolled and 58 eyes (82.9%) remained in the study at 24 months. The average age of the participants was 24.7 ± 3.8 years and 70.6% were males. At 24 months, mean UDVA changed from 0.43 ± 0.41 to 0.46 ± 0.39 logMAR (P = 0.5) and mean CDVA changed from 0.09 ± 0.10 to 0.11 ± 0.12 logMAR (P = 0.3). In measuring SE, 39.4% of cases had scissor reflex before CXL, and this frequency was reduced to 21.2% (P = 0.05) at 24 months after the procedure. Mean Kmax reduced from 46.9 ± 3.1 to 46.4 ± 2.6 D (P = 0.05). Mean Q value changed from −0.23 ± 1.9 to − 0.09 ± 1.21 (P = 0.08).

At 24 month, decreases in mesopic CS were not significant in spatial frequencies of 3 (P = 0.1), 6 (P = 0.5), 12 (P = 0.1), and 18 (P = 0.3) cycle per degree (cpd) compared to baseline [Figure 1]. The distribution of cases with increase and decrease in CS is illustrated in [Figure 2].
Figure 1: Changes in mesopic contrast sensitivity following accelerated cross-linking in progressive keratoconus patients

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Figure 2: Percent of subjects with decrease and increase in mesopic contrast sensitivity following accelerated cross-linking in progressive keratoconus patients

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Changes in ocular and corneal HOA are summarized in [Table 1]. Despite the decline, none of the HOA changed significantly. In four eyes, OPD-Scan III was not able to measure baseline aberrations due to severe corneal irregularity.
Table 1: Changes in mesopic ocular and corneal higher order aberration following accelerated cross-linking in progressive keratoconus patients

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At 2 year, mesopic CS decreased in spatial frequencies of 3 (P = 0.003), 6 (P = 0.028), 12 (P = 0.05), and 18 (P = 0.02) cpd compared to 12 months after surgery. However, change of ocular and corneal HOAs was not significant (all P > 0.05). The distributions of cases with increased and decreased ocular and corneal HOA are demonstrated in [Figure 3].
Figure 3: Percent of subjects with decrease and increase in ocular and corneal higher-order aberrations following accelerated cross-linking in progressive keratoconus patients

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Linear regression models indicated that, at baseline and 24 months after CXL, the largest contributors to ocular HOA were coma, followed by trefoil and SA (all P < 0.001). For corneal HOA, SA contributed most at baseline followed by coma and trefoil (all P < 0.001). At 24 months after CXL, dominant aberrations, in descending order, were trefoil, coma, and SA (P< 0.001).

The relationship of mesopic CS with ocular HOA and corneal HOA before and 24 months after CXL was analyzed using Pearson correlation coefficient. Correlation coefficients between ocular HOA and all four contrast spatial frequencies, as well as those between corneal HOA and CS, were <0.4 in all cases.

   Discussion Top

CXL is the only treatment for keratoconus that halts the progression of corneal protrusion and steepening. The resulting strengthening leads to the flattening and regularization of the cornea and improves vision.[14],[15] However, some studies have reported no change in Kmax.[3] In this study, we observed that, at 24 months after CXL, vision remained unchanged but refraction and Kmax decreased and corneal asphericity changed toward an oblate shape (central flattening). Therefore, the goal of CXL which is the prevention of corneal steepening was achieved in this sample.

Considering the loss of contrast [16] and increase in HOA [17] in keratoconus and inconsistency of change of quality of vision after CXL, the main objective of this study was to assess the quality of vision in two aspects, CS and HOAs, following the accelerated CXL protocol. In our 1-year follow-up, mesopic CS was affected by surgery in all spatial frequencies, except six cpd. After a temporary improvement at month 12 after CXL, they returned to baseline levels at 24 months. Lamy et al.[10] reported improved CS at 2 years after the standard protocol. In their study, the Pelli-Robson test was used under photopic conditions, and reduced keratometry confirmed treatment effectiveness. Perhaps the difference between our study and theirs is the lighting conditions. Under mesopic conditions, unlike photopic, pupil dilation leads to reduced contrast caused by HOA, and this can exist after surgery as well; just as keratometry and asphericity results pointed to corneal flattening in our study as well. The two CS testing methods have certain differences as well. CSV-1000 measures CS in four spatial frequencies separately, and as shown in [Figure 1], variations differ between the spatial frequencies of 3 and 18 cpd. In light of condition differences between the two studies, detailed comparisons cannot be drawn, but results could imply improved visual quality under photopic conditions with both protocols without causing changes in mesopic results in long term. In other words, CXL does not affect vision quality in low light conditions.

In the present study, corneal HOA had higher mean and variance than ocular HOA both before and after CXL. Mean changes in corneal HOA were also greater than ocular HOA. One could argue that compensatory mechanisms in the whole eye try to reduce aberrations. The considerable reduction in the variance of corneal HOA at 24 months compared to baseline indicated corneal regularization.

In agreement with other studies,[17],[18],[19] coma was the most dominant HOA in keratoconus patients before surgery. The most common aberration after surgery was also coma, but the greatest change was observed with SA. Although these changes were not statistically significant, they can be of clinical importance. Studies on HOA after standard CXL have reported conflicting results. Arbelaez et al.[20] reported a reduction of approximately 0.2 μm in HOA (0.02 μm coma and 0.05 μm SA) over a 1-year period, whereas Caporossi et al.[21] reported a 2-year reduction of about 1 μm (1 μm coma, SA unchanged). Using the OPD-Scan, Vinciguerra et al.[22] reported 1-year reductions of 0.03 and 0.95 μm in ocular and corneal coma and 0.02 and 0.82 μm in ocular and corneal SA, respectively. In our study, 24-month decreases in ocular and corneal coma were 0.2 and 0.6 μm and decreases in ocular and corneal SA were 0.02 and 1.7 (with 5.7 variation) μm. Since differences in pupil size can affect aberration measurements,[23] one reason for different results could be differences in aperture diameter during measurement. In the studies by Arbelaez et al. and Caporossi et al., contrary to Vinciguerra's study and the present study, aberrations were measured under photopic conditions. Comparing our results with the study by Vinciguerra et al., one could say that the two standard and accelerated protocols are not significantly different, and perhaps improved surgical techniques have caused differences in the mean change in corneal SA. On the other hand, differences in follow-up time can lead to different study results; as in our study and the study by Caporossi et al.,[23] short-term results were different from long-term results.

It has been shown that keratoconus patients have lower CS due to increased HOAs.[19] In our study, the correlation between CS and HOA was weak (<0.4) both at baseline and after CXL. In the other words, CS was not affected by aberrations. We know that CS is affected by neural factors in addition to optical factors, whereas HOAs imply show optical aberrations.

Brooks et al.[9] conducted a subjective assessment of visual function in keratoconus patients after CXL and demonstrated that the procedure has no effect on night driving, glare, and starburst. These subjective indicators can be indicative of the impact of surgery on patients' visual quality. Therefore, visual quality in low-light conditions is not affected with either protocol, and visual quality is not impaired as results of this procedure.

   Conclusion Top

Finally, visual quality included CS and higher order aberrations remained unchanged after CXL in low-light conditions and visual quality is not declined after it.

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Conflicts of interest

There are no conflicts of interest.

   References Top

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Hashemi H, Seyedian MA, Miraftab M, Fotouhi A, Asgari S. Corneal collagen cross-linking with riboflavin and ultraviolet a irradiation for keratoconus: Long-term results. Ophthalmology 2013;120:1515-20.  Back to cited text no. 2
Raiskup F, Theuring A, Pillunat LE, Spoerl E. Corneal collagen crosslinking with riboflavin and ultraviolet-A light in progressive keratoconus: Ten-year results. J Cataract Refract Surg 2015;41:41-6.  Back to cited text no. 3
Goldich Y, Marcovich AL, Barkana Y, Mandel Y, Hirsh A, Morad Y, et al. Clinical and corneal biomechanical changes after collagen cross-linking with riboflavin and UV irradiation in patients with progressive keratoconus: Results after 2 years of follow-up. Cornea 2012;31:609-14.  Back to cited text no. 4
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  [Figure 1], [Figure 2], [Figure 3]

  [Table 1]


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