Journal of Refractive Surgery

Therapeutic Refractive Surgery Supplemental Data

Long-term Clinical Outcomes of Phototherapeutic Keratectomy in Corneas With Granular Corneal Dystrophy Type 2 Exacerbated After LASIK

Ikhyun Jun, MD, PhD; Ji Won Jung, MD, PhD; Young Joon Choi, MD, PhD; Tae-im Kim, MD, PhD; Kyoung Yul Seo, MD, PhD; Eung Kweon Kim, MD, PhD

Abstract

PURPOSE:

To investigate the long-term clinical outcomes and recurrence patterns of phototherapeutic keratectomy (PTK) in patients with granular corneal dystrophy type 2 (GCD2) exacerbated after LASIK.

METHODS:

Fifty-one patients (76 eyes) with GCD2 exacerbated after LASIK who underwent PTK between January 2007 and February 2017 were included. Participants underwent ophthalmic examination, including slit-lamp microscopy, corrected distance visual acuity (CDVA), slit-lamp photography, and Fourier domain optical coherence tomography at preoperative and postoperative visits. PTK was performed using VISX S4 IR (VISX, Inc., Santa Clara, CA). Visual acuity, complications, interval, and contributing factors of recurrence were evaluated.

RESULTS:

The follow-up period ranged from 1 to 108 months (mean: 35.22 months). The mean logMAR CDVA was 0.55 ± 0.43 (Snellen equivalent 20/80) preoperatively and 0.09 ± 0.43 (Snellen equivalent 20/25) at 3 months postoperatively. Forty-five (61.6%) eyes developed biomicroscopic recurrence at a mean of 18.6 months after PTK; 20 (27.4%) eyes developed significant recurrence at a mean of 31.3 months after PTK. The flap removal group demonstrated better CDVA at 3 years after surgery and lower recurrence and complication rates than the flap conservation group. Multivariate analysis revealed that flap removal remarkably reduced the risk of both any sign of and significant recurrence.

CONCLUSIONS:

PTK improved corneal transparency and visual acuity in patients with GCD2 exacerbated after LASIK, although GCD2 eventually recurred. PTK with flap removal was superior to PTK with flap conservation in terms of visual acuity, recurrence, and complications.

[J Refract Surg. 2018;34(2):132–139.]

Abstract

PURPOSE:

To investigate the long-term clinical outcomes and recurrence patterns of phototherapeutic keratectomy (PTK) in patients with granular corneal dystrophy type 2 (GCD2) exacerbated after LASIK.

METHODS:

Fifty-one patients (76 eyes) with GCD2 exacerbated after LASIK who underwent PTK between January 2007 and February 2017 were included. Participants underwent ophthalmic examination, including slit-lamp microscopy, corrected distance visual acuity (CDVA), slit-lamp photography, and Fourier domain optical coherence tomography at preoperative and postoperative visits. PTK was performed using VISX S4 IR (VISX, Inc., Santa Clara, CA). Visual acuity, complications, interval, and contributing factors of recurrence were evaluated.

RESULTS:

The follow-up period ranged from 1 to 108 months (mean: 35.22 months). The mean logMAR CDVA was 0.55 ± 0.43 (Snellen equivalent 20/80) preoperatively and 0.09 ± 0.43 (Snellen equivalent 20/25) at 3 months postoperatively. Forty-five (61.6%) eyes developed biomicroscopic recurrence at a mean of 18.6 months after PTK; 20 (27.4%) eyes developed significant recurrence at a mean of 31.3 months after PTK. The flap removal group demonstrated better CDVA at 3 years after surgery and lower recurrence and complication rates than the flap conservation group. Multivariate analysis revealed that flap removal remarkably reduced the risk of both any sign of and significant recurrence.

CONCLUSIONS:

PTK improved corneal transparency and visual acuity in patients with GCD2 exacerbated after LASIK, although GCD2 eventually recurred. PTK with flap removal was superior to PTK with flap conservation in terms of visual acuity, recurrence, and complications.

[J Refract Surg. 2018;34(2):132–139.]

Granular corneal dystrophy type 2 (GCD2) is an autosomal dominant disorder caused by a missense mutation in the transforming growth factor β-induced gene TGFBI (p.Arg124His).1 GCD2 presents with three types of corneal deposits: granular deposits at an early stage, linear deposits with progression, and diffuse stromal haze. Patients with GCD2 exhibit acceptable corrected distance visual acuity (CDVA) in the early stages.2–5 Trauma to the central cornea, including from LASIK, laser epithelial keratomileusis, and photorefractive keratectomy (PRK),6–11 has been reported to induce the exacerbation of GCD2. In corneas with GCD2 after LASIK, increased deposits, composed mainly of hyaline materials, are located at the LASIK flap interface.11–14 To date, there have been no long-term studies investigating clinical outcomes or recurrence after phototherapeutic keratectomy (PTK) in patients with GCD2 exacerbated after LASIK. In this study, we evaluated the effect of PTK on corneas with GCD2 exacerbated after LASIK in terms of long-term clinical outcomes, recurrence rate, and associated factors.

LASIK-induced exacerbated corneal deposits in patients with GCD2 are treated using lamellar or penetrating keratoplasties,11,12 scraping of the interface opacities after lifting the flap,6,7 or PTK.7 Although keratoplasties have shown some success, rejection problems relegated the procedures to the last option. Lifting the flap and scraping out the deposits led to poor results. Although PTK has several advantages, including easy usability, repeatability, and no risk for graft failure or rejection, the number of published reports remains limited.

In this study, PTK was performed on corneas with GCD2 exacerbated after LASIK, in which LASIK flaps were conserved in 17 eyes and flaps were amputated and removed in 56 eyes for comparison.

Patients and Methods

This retrospective study was approved by the Institutional Review Board of the Yonsei University College of Medicine (Seoul, South Korea, IRB No. 4-2017-0194), and adhered to the tenets of the Declaration of Helsinki.

Patients

The clinical records of patients who underwent PTK for GCD2 exacerbated after LASIK between January 2007 and February 2017 at the Department of Ophthalmology, Yonsei University College of Medicine were reviewed by a single experienced surgeon (EKK). In each case, the diagnosis was confirmed using slit-lamp examination and DNA analysis. All included patients had the heterozygotic p.Arg124His mutation in the TGFBI gene. Eyes that required repeat PTK during follow-up after surgery were considered as new cases. Patients with uveitis, glaucoma, and other significant ocular diseases before PTK were excluded from this study. A total of 73 eyes (51 patients) were included, and patients were divided into one of two groups: the flap conservation group (17 eyes of 15 patients) and the flap removal group (56 eyes of 45 patients). Ten patients underwent PTK with flap conservation in one eye and flap removal in the opposite eye. After surgery, the patients were followed up daily until epithelial healing was complete. Routine visits were scheduled at 1, 3, 6, and 12 months after surgery, and every 6 months thereafter. Standardized eye examinations, including CDVA, manifest refraction, tonometry, slit-lamp examination, slit-lamp photographs, Scheimpflug-based corneal topography (Pentacam HR; Oculus Optikgeräte, Wetzlar, Germany), and Fourier domain optical coherence tomography (FDOCT) (RTVue-100; Optovue, Inc., Fremont, CA) were performed routinely at baseline and any visits after surgery. Central corneal thickness (CCT) was measured by FD-OCT from July 2008 (67 eyes); before that CCT was measured by Pentacam HR (6 eyes).

PTK Procedure

PTK was performed as previously reported, with some variation.3 The VISX S4 IR (VISX, Inc., Santa Clara, CA) system was used for all PTKs, with a radiant exposure of 160 mJ/cm2. Slit-lamp photographs were taken before PTK for reference. Topical proparacaine hydrochloride 0.5% (Alcaine; Alcon Laboratories, Inc., Fort Worth, TX) drops were instilled during scrubbing and draping, and the LASIK flap was lifted using a spatula. The exposed deposits on the posterior surface of the flap and on the surface of the posterior remaining stroma were scraped out using a #15 Bard-Parker knife blade. Laser ablation was performed on the surface of the posterior remaining stroma with an ablation diameter of 6 mm, with no transition zone, at a pulse rate of 10 Hz for all eyes. In the flap conservation group, the flap was subsequently repositioned after ablation on the posterior surface of the flap. In the flap removal group, the lifted flap was amputated and removed. The density and depth of the remaining diffuse stromal haze were verified after each 5- to 10-µm excimer laser ablation to prevent overtreatment. Preservative-free artificial tears were instilled every 10 µm during ablation to ensure smoothness of the ablation. PTK was performed until the diffuse stromal haze disappeared and the depth of ablation was recorded. A bandage contact lens was applied to the cornea until epithelial healing was complete. After surgery, topical ofloxacin 0.3% (Ocuflox; Samil Pharmaceutical Co., Seoul, Korea) and fluorometholone 0.1% (Ocumethelone; Samil Pharmaceutical Co.) were applied four times per day for 2 months. The dosage was gradually reduced over a period of 6 months.

Criteria for recurrence after PTK were similar to those described previously.15–17 Any sign of recurrence was considered to be present only when biomicroscopic evidence of recurrence was found, regardless of CDVA or symptoms. Recurrence was considered to be significant when the slit-lamp signs were also associated with the deterioration of two or more lines of CDVA.

Statistical Analysis

Results are presented as mean ± standard deviation (most of the data) or mean ± standard error (Figure 1). The Student's t, chi-square, or Fisher's exact test was used to determine significant differences between the two groups. Time-to-event endpoint was analyzed using the Kaplan–Meier method, and subgroups according to flap handling were compared using the log-rank test. Univariate and multivariate analyses with the enter method were performed to identify independent prognostic factors for any signs of recurrence and significant recurrence using the Cox proportional hazard regression model. Hazard ratios (HRs) and 95% confidence intervals (CIs) were determined using SPSS software (version 23.0; IBM Corporation, Armonk, NY). A P value of less than .05 was considered to be statistically significant.

LogMAR corrected distance visual acuity (CDVA) change before and after phototherapeutic keratectomy (PTK). (A) The mean logMAR CDVA of all patients according to flap. Preoperative and postoperative 3, 6, 12, and 24 months logMAR CDVA were not significantly different between the flap conservation group and the flap removal group. At 36 months after PTK, logMAR CDVA of the flap conservation group was significantly worse than that of the flap removal group. (B) The mean logMAR CDVA of patients with paired eye comparison according to flap. Similar to the overall data, logMAR CDVAs preoperatively and 3, 6, 12, and 24 months postoperatively were not different; however, postoperative 36 months logMAR CDVA was significantly different between the two groups. Data are presented as mean ± standard error; *P < .05.

Figure 1.

LogMAR corrected distance visual acuity (CDVA) change before and after phototherapeutic keratectomy (PTK). (A) The mean logMAR CDVA of all patients according to flap. Preoperative and postoperative 3, 6, 12, and 24 months logMAR CDVA were not significantly different between the flap conservation group and the flap removal group. At 36 months after PTK, logMAR CDVA of the flap conservation group was significantly worse than that of the flap removal group. (B) The mean logMAR CDVA of patients with paired eye comparison according to flap. Similar to the overall data, logMAR CDVAs preoperatively and 3, 6, 12, and 24 months postoperatively were not different; however, postoperative 36 months logMAR CDVA was significantly different between the two groups. Data are presented as mean ± standard error; *P < .05.

Results

Patient Characteristics

A total of 73 eyes (51 patients [20 men and 31 women]) underwent PTK for GCD2 exacerbated after LASIK. Table 1 summarizes the baseline characteristics of the flap conservation and flap removal groups. The follow-up period was longer in the flap conservation group than in the flap removal group because flap removal PTK was primarily performed more recently after recognition that flap removal results in a lower recurrence of deposits than flap conservation.

Characteristics of Eyes That Underwent PTK With Flap Conservation or Flap Removal in Patients With GCD2 Exacerbated After LASIKa

Table 1:

Characteristics of Eyes That Underwent PTK With Flap Conservation or Flap Removal in Patients With GCD2 Exacerbated After LASIK

Visual Outcomes

When the outcomes were evaluated in detail for the two groups (ie, flap conservation versus flap removal), logMAR CDVA of the flap removal group was significantly better than that of the flap conservation group at 3 years postoperatively, although there were no significant differences in logMAR CDVA between the two groups until 2 years after PTK (Table 2, Figure 1A). The probability of both recurrence types was significantly higher in the flap conservation group than the flap removal group (P = .01 and < .001, respectively [Table 2]). Moreover, the rate of reoperation was higher in the flap conservation group (P = .002). The complication rate was also higher in the flap conservation group compared with the flap removal group (P = .02). All 4 complication cases in the flap conservation group were listed because of epithelial ingrowth into the flap interface. In the flap removal group, corneal opacity, which is not associated with GCD2, occurred in 1 eye, and lens opacity occurred in 1 eye.

Comparison of Clinical Outcomes of the Patients With GCD2 Exacerbated After LASIK Who Underwent PTKa

Table 2:

Comparison of Clinical Outcomes of the Patients With GCD2 Exacerbated After LASIK Who Underwent PTK

Opacity Comparison Between Two Eyes That Underwent a Different Procedure in the Same Patient

In addition, 10 patients underwent PTK with flap conservation in one eye and flap removal in the opposite eye (Table A, available in the online version of this article). There were no statistically significant differences in age at PTK, preoperative CCT, or stromal ablation depth between the two groups of eyes. Similar to the results reported in Table 1, postoperative residual CCT was less and the follow-up period was shorter in the flap removal group (Table A). The logMAR CDVA was statistically better in the flap removal group eyes 3 years after surgery, demonstrating the tendency from postoperative year 1 (Table A and Figure 1B). Any signs of recurrence and significant recurrence occurred less in the flap removal group compared with the flap conservation group. The tendency toward lower rates for reoperation and complication in the flap removal group was not statistically significant, likely due to the small number of patients (Table A).

Comparison of Characteristics and Clinical Outcomes of the Patients With GCD2 After LASIK Who Underwent PTK With Flap Conservation in One Eye and Flap Removal in the Other Eyea

Table A:

Comparison of Characteristics and Clinical Outcomes of the Patients With GCD2 After LASIK Who Underwent PTK With Flap Conservation in One Eye and Flap Removal in the Other Eye

Figures 23 show representative differences in outcomes between the flap conservation and flap removal techniques.

Slit-lamp photographs revealing recurrence after phototherapeutic keratectomy (PTK) in the eye receiving flap conservation. (A) Left eye of a patient with granular corneal dystrophy type 2 exacerbated after LASIK before PTK. (B) Left eye of the same patient 10 days after PTK with flap conservation. (C) Left eye of the same patient with significant recurrence 46 months after PTK. (D) Right eye of the same patient before PTK. (E) Right eye of the same patient 10 days after PTK with flap removal. (F) Right eye of the same patient with no recurrence 36 months after PTK.

Figure 2.

Slit-lamp photographs revealing recurrence after phototherapeutic keratectomy (PTK) in the eye receiving flap conservation. (A) Left eye of a patient with granular corneal dystrophy type 2 exacerbated after LASIK before PTK. (B) Left eye of the same patient 10 days after PTK with flap conservation. (C) Left eye of the same patient with significant recurrence 46 months after PTK. (D) Right eye of the same patient before PTK. (E) Right eye of the same patient 10 days after PTK with flap removal. (F) Right eye of the same patient with no recurrence 36 months after PTK.

Slit-lamp photographs revealing the recurrence and epithelial ingrowth after phototherapeutic keratectomy (PTK) in an eye that received flap conservation. (A) Right eye of a patient with granular corneal dystrophy type 2 exacerbated after LASIK before PTK. (B) Right eye of the same patient 10 days after PTK with flap conservation. (C) Right eye of the same patient with epithelial ingrowth in inferior and significant recurrence 35 months after PTK. (D) Left eye of the same patient before PTK. (E) Left eye of the same patient 10 days after PTK with flap removal. (F) Left eye of the same patient with some recurrence 36 months after PTK.

Figure 3.

Slit-lamp photographs revealing the recurrence and epithelial ingrowth after phototherapeutic keratectomy (PTK) in an eye that received flap conservation. (A) Right eye of a patient with granular corneal dystrophy type 2 exacerbated after LASIK before PTK. (B) Right eye of the same patient 10 days after PTK with flap conservation. (C) Right eye of the same patient with epithelial ingrowth in inferior and significant recurrence 35 months after PTK. (D) Left eye of the same patient before PTK. (E) Left eye of the same patient 10 days after PTK with flap removal. (F) Left eye of the same patient with some recurrence 36 months after PTK.

Asymptomatic and Symptomatic Recurrences

Kaplan–Meier plots for any recurrence and significant recurrence are presented in Figure 4. Any sign of recurrence and significant recurrence occurred significantly faster in the flap conservation group than the flap removal group (Figures 4A–4B). The same results were observed in the contralateral eye comparison (Figures 4C–4D). Univariate analysis was performed to determine whether demographic variables or flap state affected any sign of or significant recurrence. Factors likely to have an association in the univariate analysis (P < .15) were tested using multivariate analysis to identify independent factors associated with recurrence. Results of the univariate analysis demonstrated that any recurrence was lower in the flap removal group than in the flap conservation group (P = .003). This finding was confirmed in the multivariate analysis (P = .004) (Table B, available in the online version of this article). In the contralateral eye comparison, the eyes with flap removal also showed fewer signs of recurrence and significant recurrence in the multivariate analysis (P = .04 and .03, respectively) (Table C, available in the online version of this article).

Kaplan–Meier analysis depicting the cumulative incidence of recurrence after phototherapeutic keratectomy (PTK). Cumulative probability of (A) any sign of recurrence and (B) significant recurrence in all patients. The flap conservation group exhibited a significantly faster recurrence pattern than the flap removal group in both any sign of recurrence and significant recurrence (P = .002 and < .001, respectively). Cumulative probability of (C) any sign of recurrence and (D) significant recurrence in patients with contralateral comparison. Similar to data from all patients, the flap conservation group had a significantly higher risk of relapse than the flap removal group in any sign of recurrence and significant recurrence (P = .005 and .01, respectively).

Figure 4.

Kaplan–Meier analysis depicting the cumulative incidence of recurrence after phototherapeutic keratectomy (PTK). Cumulative probability of (A) any sign of recurrence and (B) significant recurrence in all patients. The flap conservation group exhibited a significantly faster recurrence pattern than the flap removal group in both any sign of recurrence and significant recurrence (P = .002 and < .001, respectively). Cumulative probability of (C) any sign of recurrence and (D) significant recurrence in patients with contralateral comparison. Similar to data from all patients, the flap conservation group had a significantly higher risk of relapse than the flap removal group in any sign of recurrence and significant recurrence (P = .005 and .01, respectively).

Univariate and Multivariate Analyses for Any Sign of Recurrence and Significant Recurrence After PTK in Patients With GCD2 Exacerbated After LASIK (Total Patients Included)

Table B:

Univariate and Multivariate Analyses for Any Sign of Recurrence and Significant Recurrence After PTK in Patients With GCD2 Exacerbated After LASIK (Total Patients Included)

Univariate and Multivariate Analyses for Any Sign of Recurrence and Significant Recurrence in Patients With GCD2 Exacerbated by LASIK Who Underwent PTK With Flap Conservation in One Eye and Flap Removal in the Other Eye (Contralateral Eye Comparison)

Table C:

Univariate and Multivariate Analyses for Any Sign of Recurrence and Significant Recurrence in Patients With GCD2 Exacerbated by LASIK Who Underwent PTK With Flap Conservation in One Eye and Flap Removal in the Other Eye (Contralateral Eye Comparison)

Discussion

Only a few case reports on patients with GCD2 heterozygote corneas exacerbated after LASIK have been available to date.7,12,18 The data show that CDVAs immediately after PTK improved in both the flap conservation and flap removal groups, similar to those reported after PTK on virgin corneas with GCD2.15,16,18,19 These data suggest that PTK can be used on heterozygote corneas with GCD2 exacerbated after LASIK to postpone keratoplasty for a certain period of time, even though improved CDVAs would gradually decline with recurrence over time.

CDVAs in the flap removal group were well maintained until 3 years after PTK, whereas those in the flap conservation group appeared to be worsening from 1 year after the procedure. Furthermore, the recurrence rate after PTK in the flap removal group was significantly lower than that of the flap conservation group, suggesting that absence of the flap is better for maintaining clarity of the cornea. Even in the reoperated group, a higher rate of reoperation was noted in the flap conservation group: 6 cases in the flap conservation group underwent a repeat PTK (n = 5) or deep lamellar keratoplasty (n = 1) as the reoperation procedure, whereas two eyes underwent repeat PTK in the flap removal group. These results are consistent with a previous study that reported corneas with GCD2 after PRK exhibited less exacerbation than those after LASIK.10 Roh et al.9 reported that the abnormal granular clusters are mainly attached to the fibrils of the posterior surface of the flap on the GCD2 cornea exacerbated after LASIK with scanning electron microscopy. Because the flap–stromal interface after LASIK maintains dual-damaged surfaces, flap conservation would provide more opportunity for the mutated TGFBI protein to adhere or attach to the damaged stromal component, such as collagen and/or other extracellular matrix components, resulting in more severe and faster formation of deposits. This severe deposition of the mutated TGFBI protein may have influenced the adherence force of the flap to the remaining posterior stroma; therefore, the epithelial ingrowth rate after PTK in flap conservation remained high (Table 2).

Nevertheless, thin residual cornea after PTK in flap removal may induce keratectasia and/or stromal haze.20,21 We performed PTK only when the residual stromal thickness after PTK, estimated using FD-OCT,17 was greater than 250 µm, which was the minimum recommended thickness reported in previous studies.15,16 Although the cause of stromal haze (n = 1) and mild cataract (n = 1) in the flap removal group remains unclear, it may be related to deep surface ablation.17

Recurrence rates after PTK in corneal dystrophies are variable (0% to 100%) and depend on the definition of recurrence and follow-up period.15–17,19,22,23 Dinh et al.15 reported that any sign of recurrence was observed in 53% of eyes after PTK in those with granular dystrophy, with a mean time to recurrence of 31.9 months, whereas 23% of eyes exhibited significant recurrence, with a mean time to recurrence of 40.4 months. Reddy et al.16 reported a rate of 48% for any sign of recurrence and a rate of 20% for significant recurrence in granular dystrophy. Chen and Xie17 reported a mean time to recurrence of 23.7 months after PTK in eyes with granular dystrophy. In our study, the rate of any sign of recurrence was 88.2% with a mean time to recurrence of 14 months in the flap conservation group and 53.6% with a mean time to recurrence of 20.9 months in the flap removal group. The rate of significant recurrence was 70.6% with a mean time to recurrence of 23.6 months in the flap conservation group and 14.3% with a mean time to recurrence of 42.8 months in the flap removal group. The recurrence data from the flap removal group were comparable with previous studies, whereas those of the flap conservation group were higher in rate and faster in time.

Factors contributing to recurrence after PTK have been reported to be age of onset of 30 years or younger, laser ablation depth less than 50 µm, or the diameter of extension less than 5 mm, although multivariate analyses were not performed.17 However, the factor most affecting recurrence in our study was repositioning of the LASIK flap after PTK (Table B). The contralateral eye comparison reinforced this result (Table C). Age did not reflect the severity of disease in our study, probably because our patients were relatively young. We could not relate opacity with ablation depth, probably because all of the ablation depths of PTK to remove deposits in the remaining posterior stroma after LASIK were too deep to be compared with one another.

This study had some limitations. It was not designed as a prospective, randomized trial, and the number of patients in the flap conservation group was smaller than that in the flap removal group because we preferred flap removal to flap conservation after we noted the advantages of flap removal in patients after an initial, defined period of observation. The follow-up periods were variable among patients (1 to 108 months) and were longer in the flap conservation group than in the flap removal group, forcing us to adapt a Kaplan–Meier method and Cox proportional hazard regression model. Nonetheless, this study is valuable because it is the first to investigate long-term clinical outcomes of PTK in patients with GCD2 exacerbated after LASIK.

PTK in eyes with GCD2 exacerbated after LASIK is an effective treatment modality for postponing keratoplasty. PTK with flap removal can lead to relatively lower recurrence rates than with flap conservation in these patients.

References

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Characteristics of Eyes That Underwent PTK With Flap Conservation or Flap Removal in Patients With GCD2 Exacerbated After LASIKa

CharacteristicFlap ConservationFlap RemovalP
Age (y)37.12 ± 5.01 (29 to 48)38.77 ± 7.23 (28 to 63).383
Gender (male/female)7/1025/31.801
Laterality (right/left)10/725/31.305
Preoperative CDVA
  logMAR0.47 ± 0.24 (0.05 to 1.00)0.57 ± 0.47 (0.05 to 2.30).372
  Mean Snellen0.39 ± 0.20 (0.1 to 0.9)0.38 ± 0.24 (0.005 to 0.9).872
Preoperative CCT (µm)498.47 ± 34.36 (450 to 562)489.95 ± 39.21 (373 to 564).393
Stromal ablation depth (µm)34.88 ± 13.14 (20 to 65)40.21 ± 13.75 (20 to 88).162
Residual CCT (µm)423.65 ± 30.50 (376 to 479)404.36 ± 36.37 (303 to 488).037b
Follow-up (months)54.11 ± 31.93 (1 to 93)29.15 ± 29.29 (1 to 102).003b

Comparison of Clinical Outcomes of the Patients With GCD2 Exacerbated After LASIK Who Underwent PTKa

ParameterFlap ConservationFlap RemovalP
CDVA (logMAR)
  3 months0.08 ± 0.09 (0.00 to 0.30)0.10 ± 0.10 (0.00 to 0.40).591
  6 months0.07 ± 0.07 (0.00 to 0.22)0.13 ± 0.25 (0.00 to 1.30).213
  12 months0.14 ± 0.18 (0.00 to 0.70)0.09 ± 0.14 (0.00 to 0.82).357
  24 months0.28 ± 0.24 (0.05 to 0.70)0.14 ± 0.24 (0.00 to 1.00).105
  36 months0.42 ± 0.36 (0.00 to 1.30)0.11 ± 0.12 (0.00 to 0.40).002b
Any sign of recurrence (no. of eyes [%])15 (88.2)30 (53.6).010b
Significant recurrence (no. of eyes [%])12 (70.6)8 (14.3)< .001b
Reoperation (no. of eyes [%])6 (35.3)2 (3.6).002b
Complication (no. of eyes [%])4 (23.5)2 (3.6).024b

Comparison of Characteristics and Clinical Outcomes of the Patients With GCD2 After LASIK Who Underwent PTK With Flap Conservation in One Eye and Flap Removal in the Other Eyea

CharacteristicFlap ConservationFlap RemovalP
Age (y)37.90 ± 5.69 (29 to 48)40.20 ± 5.22 (34 to 51).359
Preoperative CCT (µm)491.3 ± 31.85 (450 to 544)463.5 ± 47.75 (373 to 531).143
Stromal ablation depth (µm)31.5 ± 10.28 (20 to 51)41.5 ± 19.42 (20 to 88).167
Residual CCT (µm)422.7 ± 34.13 (376 to 479)374.0 ± 38.36 (328 to 448).008b
Follow-up (mo)68.50 ± 23.39 (33 to 94)40.63 ± 31.50 (1 to 99).038b
CDVA (logMAR)
  Preoperative0.43 ± 0.19 (0.05 to 0.70)0.39 ± 0.30 (0.10 to 1.00).769
  3 months0.03 ± 0.05 (0.00 to 0.10)0.06 ± 0.07 (0.00 to 0.15).591
  6 months0.07 ± 0.03 (0.05 to 0.10)0.07 ± 0.08 (0.00 to 0.15).213
  12 months0.15 ± 0.23 (0.00 to 0.70)0.04 ± 0.04 (0.00 to 0.10).357
  24 months0.28 ± 0.28 (0.05 to 0.70)0.04 ± 0.06 (0.00 to 0.15).105
  36 months0.45 ± 0.40 (0.00 to 1.30)0.11 ± 0.13 (0.00 to 0.30).002b
Any sign of recurrence (no. of eyes [%])10 (100)6 (60).025b
Significant recurrence (no. of eyes [%])8 (80)1 (10).005b
Reoperation (no. of eyes [%])5 (50)1 (10).141
Complication (no. of eyes [%])4 (40)0 (0).087

Univariate and Multivariate Analyses for Any Sign of Recurrence and Significant Recurrence After PTK in Patients With GCD2 Exacerbated After LASIK (Total Patients Included)

CharacteristicNo.Any Sign of RecurrenceSignificant Recurrence


Univariate AnalysisMultivariate AnalysisUnivariate AnalysisMultivariate Analysis




HR (95% CI)PHR (95% CI)PHR (95% CI)PHR (95% CI)P
Age (y).34.89
  ≤40511.40 (0.70 to 2.80)1.07 (0.39 to 2.97)
  > 402211
Sex.66.78
  Male321.15 (0.62 to 2.15)1.13 (0.46 to 2.78)
  Female4111
Flap.003a.01a< .001a<.001a
  Conservation172.72 (1.40 to 5.28)2.44 (1.24 to 4.80)7.70 (2.82 to 21.01)7.70 (2.82 to 21.01)
  Removal561111
Preoperative CDVA (logMAR).57.90
  > 0.5341.19 (0.66 to 2.16)1.06 (0.43 to 2.64)
  ≤0.53911
Preoperative CCT.28.97
  ≤500440.71 (0.37 to 1.33)0.98 (0.39 to 2.51)
  > 5002911
Postoperative CCT.06.19.30
  ≤400270.56 (0.30 to 1.03)0.65 (0.35 to 1.23)0.60 (0.23 to 1.59)
  > 40046111
Stromal ablation depth (µm).79.91
  ≤35330.92 (0.50 to 1.69)0.95 (0.39 to 2.31)
  > 354011

Univariate and Multivariate Analyses for Any Sign of Recurrence and Significant Recurrence in Patients With GCD2 Exacerbated by LASIK Who Underwent PTK With Flap Conservation in One Eye and Flap Removal in the Other Eye (Contralateral Eye Comparison)

CharacteristicNo.Any Sign of RecurrenceSignificant Recurrence


Univariate AnalysisMultivariate AnalysisUnivariate AnalysisMultivariate Analysis




HR (95% CI)PHR (95% CI)PHR (95% CI)PHR (95% CI)P
Age (y).11.22.79
  ≤40122.60 (0.81 to 8.39)3.15 (0.51 to 19.59)1.21 (0.30 to 4.89)
  > 408111
Sex.88.51
  Male121.09 (0.36 to 3.34)1.60 (0.39 to 6.51)
  Female811
Flap.01a.04a.03a.03a
  Conservation105.57 (1.49 to 20.77)7.24 (1.08 to 48.75)9.86 (1.20 to 80.99)9.86 (1.20 to 80.99)
  Removal101111
Preoperative CDVA (logMAR).80.94
  > 0.591.14 (0.40 to 3.29)0.95 (0.25 to 3.54)
  ≤0.51111
Preoperative CCT.50.77
  ≤500150.67 (0.20 to 2.18)1.28 (0.26 to 6.33
  > 500511
Postoperative CCT.02a.54.76
  ≤400120.28 (0.09 to 0.84)1.85 (0.23 to 14.82)0.81 (0.22 to 3.06)
  > 4008111
Stromal ablation depth (µm).71.49
  ≤35131.22 (0.43 to 3.47)1.63 (0.41 to 6.55)
  > 35711
Authors

From The Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea (IJ, YJC, TK, KYS, EKK); Corneal Dystrophy Research Institute, Yonsei University College of Medicine, Seoul, Korea (IJ, EKK); the Department of Ophthalmology and Inha Vision Science Laboratory, Inha University School of Medicine, Incheon, Korea (JWJ); and Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea (EKK).

Dr. E. Kim is a medical advisory board member of Avellino LAB USA. The remaining authors have no financial or proprietary interest in the materials presented herein.

Supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (No. HI16C1009).

AUTHOR CONTRIBUTIONS

Study concept and design (IJ, TK, KYS, EKK); data collection (IJ, JWJ, YJC, EKK); analysis and interpretation of data (IJ, TK, KYS); writing the manuscript (IJ, EKK); critical revision of the manuscript (JWJ, YJC, TK, KYS); supervision (TK, KYS, EKK)

Correspondence: Eung Kweon Kim, MD, PhD, Department of Ophthalmology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemungu, Seoul 03722, Korea. E-mail: eungkkim@yuhs.ac

Received: July 25, 2017
Accepted: December 08, 2017

10.3928/1081597X-20171220-01

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