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Thesis (M.A.)--Boston University / Procedures to reshape the cornea to correct refractive errors have been a longstanding and fast-evolving area of interest for centuries. As recent advances in excimer laser technology allow keratorefractive treatments to deliver precise treatments with fewer associated risks and complications, the popularity of modern refractive procedures continues to grow at unprecedented rates. For this reason, it is imperative to continue correlating patient characteristics to outcomes so that refractive surgeons can more accurately foresee the results of the selected procedure. This study examined the outcomes of refractive surgeries at a full-scope ophthalmology clinic from January 2011 to November 2011. The main objectives of th is study were to determine the differences between the outcomes of LASIK vs. LASEK, Custom vs. Traditional treatment plans, myopic vs. hyperopic patients and MMC exposure vs. no MMC exposure (LASEK only). More importantly, the data was scrutinized to determine whether or not any of these treatments and/or patient characteristics correlated with poor visual outcomes or the need for an enhancement. Of the 590 myopic eyes treated with Custom LASIK, 90.85% (n=536 eyes) had UDVA of 20/20 or better, 96.10% (n=567 eyes) had UDVA of 20/25 or better and 99.32% (n=586 eyes) had UDVA of 20/40 or better. Of the 170 myopic eyes treated with Custom LASEK, 70.59% (n=120 eyes) had a UDVA of 20/20 or better, 82.94% (n=141 eyes) had a UDVA of 20/25 or better and 96.47% (n=164 eyes) had a UDVA of 20/40 or better. Of the 45 hyperopic eyes that were treated with Traditional LASIK, 44.44% (n=20 eyes) had postoperative UDVA of 20/20 or better, 62.22% (n=28 eyes) had postoperative UDVA of 20/25 or better and 82.22% (n=37 eyes) had postoperative UDVA of 20/40 or better. Of the 536 eyes receiving LASIK, 91.42% (n=490 eyes) had an UDVA of 20/20 or better, 96.46% (n=517 eyes) had an UDVA of 20/25 or better and 99.44% (n=533 eyes) had an UDVA of 20/40 or better. Of the 146 low or moderately myopic eyes receiving Custom LASEK, 74.65% (n=106 eyes) had an UDVA of 20/20 or better, 86.62% (n=123 eyes) had an UDVA of 20/25 or better and 96.48% (n=137 eyes) had an UDVA of 20/40 or better. Of the 54 highly myopic eyes treated with Custom LASIK, 85.19% (n=46 eyes) had an UDVA of 20/20 or better, 92.59% (n=50 eyes) had an UDVA of 20/25 or better, and 98.15% (n=53 eyes) had an UDVA of 20/40 or better. Of the 28 highly myopic eyes treated with Custom LASEK, 53.57% (n=15 eyes) had an UDVA of 20/20 or better, 64.29% (n=18 eyes) had an UDVA of 20/25 or better, and 96.43% (n=27 eyes) had an UDVA of 20/40 or better. An analysis of these data yields significantly greater percentages of myopic (low, moderate and high) eyes achieving 20/20 or better after treatment by Custom LASIK versus Custom LASEK. The data suggested no correlations between poor visual outcomes and/or the need for an enhancement treatment and intraoperative complications, magnitude of ametropia, pupil size, age, treatment type, and treatment plan. All of the LASEK patients who underwent an enhancement treatment were exposed to MMC during their original procedure. Hyperopic patients displayed significantly reduced visual outcomes than comparable myopic treatments. Future studies should investigate similar preoperative characteristics and attempt to correlate them to results to improve predictability and, thus, visual outcomes.

Wavefront-guided (WFG) laser in situ keratomileusis (LASIK) differs from conventional surgery by applying a refined algorithm for tissue removal, based on information from preoperative wavefront aberration data. Since the introduction of this technology, there have been few investigations comprehensively reporting outcomes, particularly for hyperopic treatments. This thesis aimed to determine the impact of myopic and hyperopic WFG LASIK on visual acuity, contrast sensitivity, higher order aberrations and subjective ratings, as well as determine the relationship between these outcome measures. Bilateral WFG LASIK was performed on 324 myopic eyes (162 subjects) and 62 hyperopic eyes (31 subjects). High contrast (HC) and low contrast (LC) best-corrected visual acuity (BCVA) and contrast sensitivity were assessed using ETDRS charts and vertical sinusoidal gratings, respectively. Higher order ocular aberrations were measured using a Shack-Hartmann wavefront sensor and analyzed across a 5.0 mm pupil. Subjective ratings were assessed using a closed-ended categorical questionnaire. Assessments were conducted prior to surgery and at three and six months postoperatively. WFG LASIK had minimal impact on BCVA and contrast sensitivity; however there was an impact on the magnitude and profile of higher order aberrations, which differed between the myopic and hyperopic groups. There was a greater increase in higher order aberrations for the hyperopic group, who also had a tendency to have lower visual outcomes and worse subjective ratings. Despite these results, there were no associations between subjective ratings and higher order aberrations, LC BCVA or contrast sensitivity for both groups and a clear understanding of the relationship between these outcome measures was not apparent. Factor analysis revealed a variety of factors that contributed to the outcome measures for this data set, with the three main factors being: subjective ratings, vision and optical quality. In conclusion, WFG LASIK had excellent outcomes in terms of visual acuity, contrast sensitivity, and subjective ratings, despite an increase in higher order aberrations compared with those found prior to surgery. Hyperopic outcomes were slightly worse than myopic outcomes. Further investigation is required to determine the impact of higher order aberrations on visual acuity, contrast sensitivity and subjective ratings, as well as the relationship between these measures.

Wavefront-guided (WFG) laser in situ keratomileusis (LASIK) differs from conventional surgery by applying a refined algorithm for tissue removal, based on information from preoperative wavefront aberration data. Since the introduction of this technology, there have been few investigations comprehensively reporting outcomes, particularly for hyperopic treatments. This thesis aimed to determine the impact of myopic and hyperopic WFG LASIK on visual acuity, contrast sensitivity, higher order aberrations and subjective ratings, as well as determine the relationship between these outcome measures. Bilateral WFG LASIK was performed on 324 myopic eyes (162 subjects) and 62 hyperopic eyes (31 subjects). High contrast (HC) and low contrast (LC) best-corrected visual acuity (BCVA) and contrast sensitivity were assessed using ETDRS charts and vertical sinusoidal gratings, respectively. Higher order ocular aberrations were measured using a Shack-Hartmann wavefront sensor and analyzed across a 5.0 mm pupil. Subjective ratings were assessed using a closed-ended categorical questionnaire. Assessments were conducted prior to surgery and at three and six months postoperatively. WFG LASIK had minimal impact on BCVA and contrast sensitivity; however there was an impact on the magnitude and profile of higher order aberrations, which differed between the myopic and hyperopic groups. There was a greater increase in higher order aberrations for the hyperopic group, who also had a tendency to have lower visual outcomes and worse subjective ratings. Despite these results, there were no associations between subjective ratings and higher order aberrations, LC BCVA or contrast sensitivity for both groups and a clear understanding of the relationship between these outcome measures was not apparent. Factor analysis revealed a variety of factors that contributed to the outcome measures for this data set, with the three main factors being: subjective ratings, vision and optical quality. In conclusion, WFG LASIK had excellent outcomes in terms of visual acuity, contrast sensitivity, and subjective ratings, despite an increase in higher order aberrations compared with those found prior to surgery. Hyperopic outcomes were slightly worse than myopic outcomes. Further investigation is required to determine the impact of higher order aberrations on visual acuity, contrast sensitivity and subjective ratings, as well as the relationship between these measures.

The principal work in this thesis describes the investigation of the impact that alterations to ocular aberrations following refractive surgery have on the accommodative mechanism. A series of prospective studies were conducted with healthy adults (n=36) that had chosen to undergo refractive surgery at Manchester Royal Eye Hospital. A variety of monocular accommodative functions were assessed prior to surgery and then at one and three months following surgery on the same cohort of patients. Accommodative functions included amplitude of accommodation, accommodative facility (at 6m and 0.4m) including positive and negative response times, and accommodative stimulus-response functions. Dynamic accommodation responses were examined in a subgroup (n=10) at three months following refractive surgery and compared to an age-matched emmetropic control group (n=10) to evaluate differences in latency, amplitude, time constant and peak velocity of accommodation and disaccommodation. During the studies, ocular aberrations were concurrently measured to determine whether alterations to aberrations could help explain any observed changes in accommodative functions. Evaluation of visual, refractive and questionnaire outcome measures indicated that the patient cohort underwent successful surgery. Following surgery, significant alterations to a number of accommodative functions were discovered. Mean subjective ocular amplitude of accommodation increased by approximately 0.50D (p<0.05), mean stimulus-response function gradient decreased by approximately 10% (p<0.05) and distance facility rate increased by approximately 2-3 cycles/minute (p<0.05). Significant correlation was found between the change in accommodative stimulus-response function gradient, and the change in spherical aberration following surgery (p<0.05). Significant differences were also found in the parameters of accommodative dynamics, although some of these factors may be explained by refractive error differences between the refractive surgery patients (pre-operative myopes) and the emmetropic control group. The results suggest that alterations to aberrations following refractive surgery may be capable of influencing elements of the accommodation response. Additional studies were conducted to investigate the changes in aberrations during accommodation (n=31 subjects), and explore the contribution of the tear film (n=19 subjects) to higher order aberrations in eyes that have undergone refractive surgery. The results suggested that the rate of change in aberrations during accommodation is not affected by refractive surgery, but that the pattern of aberrations induced by post-blink tear film changes may differ in patients that have undergone refractive surgery. A further study is presented which investigated the form of the accommodative stimulus-response function to grating target of different spatial frequencies in groups of myopic (n=10) and emmetropic (n=10) participants recruited from among the staff and students at The University of Manchester. Both refractive groups appeared to show similar accommodative behavior, however the dominant feature of the data in both groups was between subject variation.

BACKGROUND: Laser vision correction (LVC) developed as a more permanent alternative to other forms of refractive error correction. In the last several decades, visual outcomes of corneal refractive surgeries like LVC have improved dramatically with the discovery of new technologies and techniques designed to make the patient experience more comfortable and worthwhile. LVC has been shown to safely and effectively treat refractive errors in myopic and hyperopic eyes, with gradually improving outcomes and safety measures. However, it is important to note whether specific excimer lasers impart the same level of safe, effective treatments for patients as technology advances. OBJECTIVE: This study aims to identify whether any statistically significant difference exists in the visual and refractive outcomes of hyperopic laser vision correction using two excimer laser platforms, the VISX STAR S4 IR® and the WaveLight® EX500, and to determine whether either laser shows any statistically significant difference in the rate of repeat surgery within one year post-operatively. METHODS: Using EMR data collected from December 2008 through December 2016, distance and near visual acuity outcomes for hyperopic eyes treated with LASIK, LASEK, or PRK were compared at one month and up to one year post-operatively. Distance eyes were compared separately from monovision (near-targeted) eyes for visual acuity; however, if manifest refraction post-operative data were available, they were used to identify whether any difference existed in the refractive outcomes in either category. The number of enhancements (repeat surgeries) was also tabulated. X2 Tests of Independence were used to determine statistical significance. RESULTS: Visual acuity outcomes in distance eyes at one month post-operatively showed similar trends between the two lasers, with 54% of the 267 VISX- and 60% of the 119 EX500-treated eyes presenting with UCVA of 20/20 or better. Eyes available for follow-up within one year post-operatively kept with this trend; 98 (51%) VISX- and 58 (67%) EX500-treated, eyes had UCVA measured at 20/20 or better. For monovision (treated for reading vision) eyes, 29 (47%) eyes and 19 (54%) of VISX- and EX500-treated eyes, respectively, read J1+ by one month post-operatively. By one year, 16 (39%) and 3 (21%) of available eyes read J1+ after treatment with the VISX and EX500 respectively. The relative enhancement rate was 7.82% (28 eyes) on the VISX and 4.19% (7 eyes) on the EX 500. CONCLUSION: Overall, visual outcomes of laser vision correction for hyperopic patients did not differ consistently between the two lasers. Only distance-treated eyes measured up to one year post-operatively showed a statistically significant difference between the two lasers. The visual and, more importantly, the refractive outcomes were statistically similar at both one month and up to one year post-operatively irrespective of treatment type. Enhancement rate between the two lasers also showed no differences. Both lasers are similarly safe and effective for treating hyperopia and hyperopic astigmatism. / 2018-01-11T00:00:00Z

This thesis proposes and tests an individually customizable model of the human crystalline lens. This model will be crucial in developing both research on the human eye and driving diagnostic tools to help plan and treat optical issues, such as those requiring refractive surgery. This thesis attempts to meet two goals: first, it will determine whether this new lens model can reproduce the major aberrations of real human eyes using a computational framework. Second, it will use clinical information to measure how well this model is able to predict post-operation results in refractive surgery, attempting to meet clinical standards of error. The model of the crystalline lens proposed within this thesis is shown to be valid, as it is able to both reproduce individual patient's optical information, and correctly predicts the optical results of a refractive surgery of an individual human eye within clinical standards of error.

The purpose of this thesis is to describe the development of an anatomically based, young adult eye model, which includes a crystalline lens with a gradient refractive index (GRIN). This model will then be used to investigate the effect of laser refractive surgery. The first step in this process involved developing a symmetrical eye model that was found to be a better predictor of empirical longitudinal spherical aberration than any previous model. Myopia was simulated by either a purely axial or refractive technique. While these models were found to be good predictors of the spherical aberration measured in young adults, they did not predict the total amount of high-order aberrations. The techniques used to simulate a single type of myopia caused the myopic models to become anatomically inaccurate. To improve the eye models a biconic surface was used to quantify the anterior corneal shape as a function of myopia. A method to describe the refractive error and biconic shape parameters in Jackson Cross Cylinder terms was implemented to determine correlations. Results indicate that a biconic accurately models the average shape of the anterior corneal surface as a function of myopia. Adopting the biconic model for the anterior corneal surface and adding average misalignments of the ocular components transformed the models from symmetrical to asymmetrical. Refractive error was now simulated by the anatomically accurate changes in both the anterior corneal shape and axial length. The asymmetrical aberrations resulted from the misalignment of the ocular components and provided a good prediction of average empirical aberrations but underestimated the aberrations of individual subjects. Photorefractive keratectomy, a form of laser refractive surgery, was simulated by theoretically calculated and by empirically measured changes in the shape of the anterior corneal surface. Applying the change in anterior corneal shape to the asymmetrical models was used to develop postoperative models. Changes in corneal shape and model aberrations attributed to theoretical calculations do not match empirical observations. The prediction of increased high-order aberrations in postoperative models based on empirically measured changes in the anterior corneal topography was similar to clinical results. Average anatomically based, GRIN eye models have been developed that accurately predict the average aberrations of emmetropic and myopic young adults. These models underestimate the asymmetrical and total high-order aberrations that have been measured in individual subjects but are still useful for investigating the average effects of procedures like refractive surgery.

The purpose of this thesis is to describe the development of an anatomically based, young adult eye model, which includes a crystalline lens with a gradient refractive index (GRIN). This model will then be used to investigate the effect of laser refractive surgery. The first step in this process involved developing a symmetrical eye model that was found to be a better predictor of empirical longitudinal spherical aberration than any previous model. Myopia was simulated by either a purely axial or refractive technique. While these models were found to be good predictors of the spherical aberration measured in young adults, they did not predict the total amount of high-order aberrations. The techniques used to simulate a single type of myopia caused the myopic models to become anatomically inaccurate. To improve the eye models a biconic surface was used to quantify the anterior corneal shape as a function of myopia. A method to describe the refractive error and biconic shape parameters in Jackson Cross Cylinder terms was implemented to determine correlations. Results indicate that a biconic accurately models the average shape of the anterior corneal surface as a function of myopia. Adopting the biconic model for the anterior corneal surface and adding average misalignments of the ocular components transformed the models from symmetrical to asymmetrical. Refractive error was now simulated by the anatomically accurate changes in both the anterior corneal shape and axial length. The asymmetrical aberrations resulted from the misalignment of the ocular components and provided a good prediction of average empirical aberrations but underestimated the aberrations of individual subjects. Photorefractive keratectomy, a form of laser refractive surgery, was simulated by theoretically calculated and by empirically measured changes in the shape of the anterior corneal surface. Applying the change in anterior corneal shape to the asymmetrical models was used to develop postoperative models. Changes in corneal shape and model aberrations attributed to theoretical calculations do not match empirical observations. The prediction of increased high-order aberrations in postoperative models based on empirically measured changes in the anterior corneal topography was similar to clinical results. Average anatomically based, GRIN eye models have been developed that accurately predict the average aberrations of emmetropic and myopic young adults. These models underestimate the asymmetrical and total high-order aberrations that have been measured in individual subjects but are still useful for investigating the average effects of procedures like refractive surgery.

Overview: Optical concepts as they relate to the ophthalmologic correction of vision in corneal laser vision correction and intraocular lens design was examined. Purpose: The interaction between the excimer laser and residual corneal tissue in laser vision correction produces unwanted side effects. Understanding the origin of these artifacts can lead to better procedures. Furthermore, accommodating intraocular lenses offer a potential for eliminating presbyopia. Understanding the properties of a new accommodating intraocular lens incorporating a deformable interface may lead to advances in cataract surgery. Introduction: Corneal surface irregularities following laser refractive procedures are commonly seen. They regularly result in a patient’s decreased best corrected visual acuity and decreased contrast sensitivity. These changes are only seen in biologic tissue and the etiology has been elusive. A thermal response has been theorized and was investigated in this research. In addition, intraocular lenses using a mechanically deforming interface to change their power in order to duplicate natural accommodation have been developed. The deforming interface(s) induce optical aberrations due to irregular deformations. Design efforts have centered on minimizing these deformations. Both of the ophthalmic applications have been analyzed using finite element analysis (FEA) to understand their inherent optical properties. Methods: FEA modeling of thermal theory has been applied to verify that excimer laser induced collagen contraction creates corneal surface irregularities and central islands. A mathematical model which indicates the viability of the theory was developed. The modeling results were compared to post ablation changes in eyes utilizing an excimer (ArF 193 nm), as well as non-ablative thermal heating in eyes with a CO₂ laser. Addition modeling was performed on an Intraocular lens prototype measuring of actuation force, lens power, interface contour, optical transfer function, and visual Strehl ratio. Prototype verified mathematical models were utilized to optimize optical and mechanical design parameters to maximize the image quality and minimize the required force. Results: The predictive model shows significant irregular central buckling formation and irregular folding. The amount of collagen contraction necessary to cause significant surface changes is very small (0.3%). Uniform scanning excimer laser ablation to corneal stroma produces a significant central steepening and peripheral flattening in the central 3mm diameter. Isolated thermal load from uniform CO₂ laser irradiation without ablation also produces central corneal steepening and paracentral flattening in the central 3mm diameter. The iterative mathematical modeling based upon the intraocular lens prototype yielded maximized optical and mechanical performance through varied input mechanical and optical parameters to produce a maximized visual Strehl ratio and a minimized force requirement. Conclusions: The thermal load created by laser irradiation creates a characteristic spectrum of morphologic changes on the porcine corneal stromal surface which correlates to the temperature rise and is not seen inorganic, isotropic material. The highly similar surface changes seen with both lasers are likely indicative of temperature induced transverse collagen fibril contraction and stress re-distribution. Refractive procedures which produce significant thermal load should be cognizant of these morphological changes. The optimized intraocular lens operates within the physiologic constraints of the human eye including the force available for full accommodative amplitude using the eye’s natural focusing feedback, while maintaining image quality in the space available. Optimized optical and mechanical performance parameters were delineated as those which minimize both asphericity and actuation pressure. The methodology combines a multidisciplinary basic science approach from biomechanics, optical science, and ophthalmology to optimize an intraocular lens design suitable for preliminary trials.