Corneal nerves in refractive surgery and dry eye

This study aimed to investigate the morphology and function of corneal sensory nerves in 1) patients after corneal refractive surgery and 2) patients with dry eye due to Sjögren's syndrome. A third aim was to explore the possible correlation between cytokines detected in tears and development of post-PRK subepithelial haze. The main methods used were tear fluid ELISA analysis, corneal in vivo confocal microscopy, and noncontact esthesiometry. The results revealed that after PRK a positive correlation exists between the regeneration of subbasal nerves and the thickness of regenerated epithelium. Pre- or postoperative levels of the tear fluid cytokines TGF-β1, TNF-α, or PDGF-BB did not correlate with the development of corneal haze objectively estimated by in vivo confocal microscopy 3 months after PRK. After high myopic LASIK, a discrepancy between subjective dry eye symptoms and objective signs of dry eye was observed. The majority of patients reported ongoing dry eye symptoms even 5 years after LASIK, although no objective clinical signs of dry eye were apparent. In addition, no difference in corneal sensitivity was observed between these patients and controls. Primary Sjögren's syndrome patients presented with corneal hypersensitivity, although their corneal subbasal nerve density was normal. However, alterations in corneal nerve morphology (nerve sprouting and thickened stromal nerves) and an increased number of antigen-presenting cells among subbasal nerves were observed, implicating the presence of an ongoing inflammation. Based on these results, the relationship between nerve regeneration and epithelial thickness 3 months after PRK appears to reflect the trophic effect of corneal nerves on epithelium. In addition, measurement of tear fluid cytokines may not be suitable for screening patients for risk of scar (haze) formation after PRK. Presumably, at least part of the symptoms of "LASIK-associated dry eye" are derived from aberrantly regenerated and abnormally functioning corneal nerves. Thus, they may represent a form of corneal neuropathy or "phantom pain" rather than conventional dry eye. Corneal nerve alterations and inflammatory findings in Sjögren's syndrome offer an explanation for the corneal hypersensitivity or even chronic pain or hyperalgesia often observed in these patients. In severe cases of disabling chronic pain in patients with dry eye or after LASIK, when conventional therapeutic possibilities fail to offer relief, consultation of a physician specialized in pain treatment is recommended.

Excimer laser refractive surgery : corneal wound healing and clinical results

Although the first procedure in a seeing human eye using excimer laser was reported in 1988 (McDonald et al. 1989, O'Connor et al. 2006) just three studies (Kymionis et al. 2007, O'Connor et al. 2006, Rajan et al. 2004) with a follow-up over ten years had been published when this thesis was started. The present thesis aims to investigate 1) the long-term outcomes of excimer laser refractive surgery performed for myopia and/or astigmatism by photorefractive keratectomy (PRK) and laser-in situ- keratomileusis (LASIK), 2) the possible differences in postoperative outcomes and complications when moderate-to-high astigmatism is treated with PRK or LASIK, 3) the presence of irregular astigmatism that depend exclusively on the corneal epithelium, and 4) the role of corneal nerve recovery in corneal wound healing in PRK enhancement. Our results revealed that in long-term the number of eyes that achieved uncorrected visual acuity (UCVA)≤0.0 and ≤0.5 (logMAR) was higher after PRK than after LASIK. Postoperative stability was slightly better after PRK than after LASIK. In LASIK treated eyes the incidence of myopic regression was more pronounced when the intended correction was over >6.0 D and in patients aged <30 years.Yet the intended corrections in our study were higher for LASIK than for PRK eyes. No differences were found in percentages of eyes with best corrected visual acuity (BCVA) or loss of two or more lines of visual acuity between PRK and LASIK in the long-term. The postoperative long-term outcomes of PRK with two different delivery systems broad beam and scanning laser were compared and revealed no differences. Postoperative outcomes of moderate-to-high astigmatism yielded better results in terms of UCVA and less compromise or loss of two more lines of BCVA after LASIK that after PRK.Similar stability for both procedures was revealed. Vector analysis showed that LASIK outcomes tended to be more accurate than PRK outcomes, yet no statistically differences were found. Irregular astigmatism secondary to recurrent corneal erosion due to map-dot-fingerprint was successfully treated with phototherapeutic keratectomy (PTK). Preoperative videokeratographies (VK) showed irregular astigmatism. However, postoperatively, all eyes showed a regular pattern. No correlation was found between pre- and postoperative VK patterns. Postoperative outcomes of late PRK in eyes originally subjected to LASIK showed that all (7/7) eyes achieved UCVA ≤0.5 at last follow-up (range 3 — 11 months), and no eye lost lines of BCVA. Postoperatively all eyes developed and initial mild haze (0.5 — 1) into the first month. Yet, at last follow-up 5/7 eyes showed a haze of 0.5 and this was no longer evident in 2/7 eyes. Based on these results, we demonstrated that the long-term outcomes after PRK and LASIK were safe and efficient, with similar stability for both procedures. The PRK outcomes were similar when treated by broad-beam or scanning slit laser. LASIK was better than PRK to correct moderate-to-high astigmatism, yet both procedures showed a tendency of undercorrection. Irregular astigmatism was proven to be able to depend exclusively from the corneal epithelium. If this kind of astigmatism is present in the cornea and a customized PRK/LASIK correction is done based on wavefront measurements an irregular astigmatism may be produced rather than treated. Corneal sensory nerve recovery should have an important role in the modulation of the corneal wound healing and post-operative anterior stromal scarring. PRK enhancement may be an option in eyes with previous LASIK after a sufficient time interval that in at least 2 years.

Importance of anterior segment tomography for the diagnosis of corneal ectasia

Purpose: The methodology currently used for interpretation of the cornea and anterior segment tomography for the diagnosis of corneal ectasia and its susceptibility. Methods: Description of the methodology and clinical interpretation of corneal and anterior segment tomography indexes; report of three cases demonstrating the importance of this new diagnostic tool (Pentacam HR (R)) in ophthalmological practice. Conclusion: The use of corneal and anterior segment tomography seems to be an effective method to increase the sensitivity and specificity for the diagnosis and early detection of corneal ectasia.

Corneal wavefront-guided photorefractive keratectomy with mitomycin-C for hyperopia after radial keratotomy: Two-year follow-up

PURPOSE: To assess corneal wavefront-guided photorefractive keratectomy (PRK) to correct hyperopia after radial keratotomy (RK). SETTING: Sadalla Amin Ghanem Eye Hospital, Joinville, Santa Catarina, Brazil. DESIGN: Case series. METHODS: Excimer laser corneal wavefront-guided PRK with intraoperative mitomycin-C (MMC) 0.02% was performed. Main outcome measures were uncorrected (UDVA) and corrected (CDVA) distance visual acuities, spherical equivalent (SE), corneal aberrations, and haze. RESULTS: The mean time between RK and PRK in the 61 eyes (39 patients) was 18.8 years +/- 3.8 (SD). Before PRK, the mean SE was +4.17 +/- 1.97 diopters (D); the mean astigmatism, -1.39 +/- 1.04 D; and the mean CDVA, 0.161 +/- 0.137 logMAR. At 24 months, the mean values were 0.14 +/- 0.99 D (P<.001), -1.19 +/- 1.02 D (P=.627), and 0.072 +/- 0.094 logMAR (P<.001), respectively; the mean UDVA was 0.265 +/- 0.196 (P<.001). The UDVA was 20/25 or better in 37.7% of eyes and 20/40 or better in 68.9%. The CDVA improved by 1 or more lines in 62.3% of eyes. Two eyes (3.3%) lost 2 or more lines, 1 due to corneal ectasia. Thirty eyes (49.2%) were within +/- 0.50 D of intended SE and 45 (73.8%) were within +/- 1.00 D. From 6 to 24 months, the mean SE regression was +0.39 D (P<.05). A significant decrease in coma, trefoil, and spherical aberration occurred. Three eyes developed peripheral haze more than grade 1. CONCLUSION: Corneal wavefront-guided PRK with MMC for hyperopia after RK significantly improved UDVA, CDVA, and higher-order corneal aberrations with a low incidence of visually significant corneal haze.

Algorithm for Correcting the Keratometric Error in the Estimation of the Corneal Power in Eyes With Previous Myopic Laser Refractive Surgery

Purpose: To calculate theoretically the errors in the estimation of corneal power when using the keratometric index (nk) in eyes that underwent laser refractive surgery for the correction of myopia and to define and validate clinically an algorithm for minimizing such errors. Methods: Differences between corneal power estimation by using the classical nk and by using the Gaussian equation in eyes that underwent laser myopic refractive surgery were simulated and evaluated theoretically. Additionally, an adjusted keratometric index (nkadj) model dependent on r1c was developed for minimizing these differences. The model was validated clinically by retrospectively using the data from 32 myopic eyes [range, −1.00 to −6.00 diopters (D)] that had undergone laser in situ keratomileusis using a solid-state laser platform. The agreement between Gaussian (PGaussc) and adjusted keratometric (Pkadj) corneal powers in such eyes was evaluated. Results: It was found that overestimations of corneal power up to 3.5 D were possible for nk = 1.3375 according to our simulations. The nk value to avoid the keratometric error ranged between 1.2984 and 1.3297. The following nkadj models were obtained: nkadj= −0.0064286r1c + 1.37688 (Gullstrand eye model) and nkadj = −0.0063804r1c + 1.37806 (Le Grand). The mean difference between Pkadj and PGaussc was 0.00 D, with limits of agreement of −0.45 and +0.46 D. This difference correlated significantly with the posterior corneal radius (r = −0.94, P < 0.01). Conclusions: The use of a single nk for estimating the corneal power in eyes that underwent a laser myopic refractive surgery can lead to significant errors. These errors can be minimized by using a variable nk dependent on r1c.

Comparison of the predictability of refractive cylinder correction by laser in situ keratomileusis in eyes with low or high ocular residual astigmatism

Purpose: To compare the manifest refractive cylinder (MRC) predictability of myopic astigmatism laser in situ keratomileusis (LASIK) between eyes with low and high ocular residual astigmatism (ORA). Setting: London Vision Clinic, London, United Kingdom. Design: Retrospective case study. Methods: The ORA was considered the vector difference between the MRC and the corneal astigmatism. The index of success (IoS), difference vector ÷ MRC, was analyzed for different groups as follows: stage 1, low ORA (ORA ÷ MRC <1), high ORA (ORA ÷ MRC ≥1); stage 2, low ORA group reduced to match the high ORA group for MRC; stage 3, grouped by ORA magnitude with low ORA (<0.50 diopters [D]), mid ORA (0.50 to 1.24 D), and high ORA (≥1.25 D); stage 4, high ORA group subdivided into low (<0.75 D) and high (≥0.75 D) corneal astigmatism. Results: For stage 1, the mean preoperative MRC and mean IoS were −1.32 D ± 0.65 (SD) (range −0.55 to −3.77 D) and 0.27, respectively, for low ORA and −0.79 ± 0.20 D (range −0.56 to −2.05 D) and 0.37, respectively, for high ORA. For stage 2, the mean IoS increased to 0.32 for low ORA. For stage 3, the mean IoS was 0.28, 0.29, and 0.31 for low ORA, mid ORA, and high ORA, respectively. For stage 4, the mean IoS was 0.20 for high ORA/low corneal astigmatism and 0.35 for high ORA/high corneal astigmatism. Conclusions: The MRC predictability was slightly worse in eyes with high ORA when grouped by the ORA ÷ MRC. Matching for the MRC and grouping by ORA magnitude resulted in similar predictability; however, eyes with high ORA and high corneal astigmatism were less predictable.

Wavefront-Guided Laser Treatment Using a High-Resolution Aberrometer to Measure Irregular Corneas: A Pilot Study

PURPOSE: To evaluate in a pilot study the visual, refractive, corneal topographic, and aberrometric changes after wavefront-guided LASIK or photorefractive keratectomy (PRK) using a high-resolution aberrometer to calculate the treatment for aberrated eyes. METHODS: Twenty aberrated eyes of 18 patients undergoing wavefront-guided LASIK or PRK using the VISX STARS4IR excimer laser and the iDesign aberrometer (Abbott Medical Optics, Inc., Santa Ana, CA) were enrolled in this prospective study. Three groups were differentiated: keratoconus post-CXL group including 11 keratoconic eyes (10 patients), post-LASIK group including 5 eyes (5 patients) with previous decentered LASIK treatments, and post-RK group including 4 eyes (3 patients) with previous radial keratotomy. Visual, refractive, contrast sensitivity, corneal topographic, and ocular aberrometric changes were evaluated during a 6-month follow-up. RESULTS: An improvement in uncorrected (UDVA) and corrected visual acuity (CDVA) associated with a reduction in the spherical equivalent was observed in the three groups, but was only statistically significant in the keratoconus post-CXL and post-LASIK groups (P ≤ .04). All eyes gained one or more lines of CDVA after surgery. Improvements in contrast sensitivity were observed in the three groups, but they were only statistically significant in the keratoconus post-CXL and post-LASIK groups (P ≤ .04). Regarding aberrations, a reduction was observed in trefoil aberrations in the keratoconus post-CXL group (P = .05) and significant reductions in higher-order and primary coma aberrations in the post-LASIK group (P = .04). CONCLUSIONS: Wavefront-guided laser enhancements using the evaluated platform seem to be safe and effective to restore the visual function in aberrated eyes.

Diadenosine polyphosphates after laser in situ keratomileusis and photorefractive keratectomy refractive techniques

Purpose:  To study the concentrations of diadenosine polyphosphates in the ocular surface after PRK and LASIK. Methods:  Sixty-one patients (30 males and 31 females) with ages ranging from 20 to 63 (34.04 ± 9.13 years) were recruited in Balear Institute of Ophthalmology, Palma de Mallorca, Spain. LASIK was performed in 92 eyes of 46 patients and PRK in 25 eyes of 15 patients. Variations in the levels of diadenosine polyphosphate (Ap4A and Ap5A), Schirmer I (Jones test), TBUT, corneal staining together with the Dry Eye Questionnaire to evaluate discomfort and dryness were studied. All tests were performed at the preoperative visit and at 1-day, 2-week, 1-month and 3-month postoperative visits. Results:  Ap4A showed a 5 and 3.5 fold increase at the 1-day visit for LASIK and PRK, respectively. LASIK patients continued having higher statistically significant concentrations (p = 0.01) all over the follow-up. Ap5A showed no significant differences at any visit. Tear volume decreased during the 3 months in LASIK. The PRK cases had a normal volume at 1 month. TBUT in LASIK increased at the 1-day visit (p = 0,002) and decreased from the 2 weeks onwards and for the PRK, decreased by a 35% at the 1-day visit and kept reduced for a month. Discomfort only increased at the 1-day visit (p = 0.007). Dryness frequency was similar in all visits. Conclusions:  Ap4A levels only are increased in refractive surgery patients during the first day after the surgery. This increasing suggests that Ap4A may help accelerating the healing process.

Comparison of Intraocular Pressure before and after Laser In Situ Keratomileusis Refractive Surgery Measured with Perkins Tonometry, Noncontact Tonometry, and Transpalpebral Tonometry

Purpose. To compare the intraocular pressure (IOP) before and after Laser In Situ Keratomileusis (LASIK), measured by Diaton, Perkins, and noncontact air pulse tonometers. Methods. Fifty-seven patients with a mean age of 34.88 were scheduled for myopia LASIK treatment. Spherical equivalent refraction (SER), corneal curvature (K), and central corneal thickness (CCT) and superior corneal thickness (SCT) were obtained before and after LASIK surgery. IOP values before and after surgery were measured using Diaton, Perkins, and noncontact air pulse tonometers. Results. The IOP values before and after LASIK surgery using Perkins tonometer and air tonometers were statistically significant (). However, no significant differences were found () for IOP values measured with Diaton tonometer. CCT decreases significantly after surgery () but no statistical differences were found in SCT (). Correlations between pre- and postsurgery were found for all tonometers used, with and for the air pulse tonometer, and for Perkins, and and for Diaton. Conclusion. Transpalpebral tonometry may be useful for measuring postsurgery IOP after myopic LASIK ablation because this technique is not influenced by the treatment.