10_09 smart_3:layout

10_09 SMART_3:Layout 1 9/23/09 12:52 AM Page 24 The SMART Study:
Background, Rationale,
and Baseline Results
This long-term longitudinal study aims to answer the
question of whether ortho-k can control myopia.
Dr. Eiden is co-founder ofEyeVis Eye and Vision Re-search Institute and presi-dent of a private grouppractice in Illinois. He has afinancial interest in Alterna-tive Vision Solutions, LLC, is Myopia is the most this 6- to 14-year-old age group could impact 40 million or more adults in eye disorder in the the United States because of fewer world and contin- ocular health risks with low (rather ues to represent a than high) myopic refractive error.
worldwide public health problem. Es-timates indicate that its prevalence in a consultant or advisor to the United States is 25 percent (Sper- Myopia Control Studies Myopia pro-
CIBA Vision, CooperVision,SynergEyes, Alcon, and Spe- duto et al, 1983; Vitale et al, 2008; gression is primarily due to elonga- cialEyes and has received re- Wang et al, 1994; Katz et al, 1997; tion of the axial length (AL). If search funds from Vistakon, Goss and Winkler, 1983; Kempen et myopia is to be controlled during its CooperVision, and B&L.
al, 2004). It is associated with an in- development, the correcting device Dr. Davis is co-founder of creased risk for visual loss, including must reduce the progression of eye EyeVis Eye and Vision Re- accounting for 5.6 percent of blind- growth. Walline et al (2008) found search Institute. He practices ness among U.S. schoolchildren that over a three-year period, soft in a suburb outside Chicago.
He is an advisor or consul- (Tokoro, 1982). Myopia remains one contact lenses did not have any signif- tant to CooperVision and of the most prevalent ocular disorders icant effect on slowing AL progres- SynergEyes, has received re- for which a uniformly acceptable so- sion in young lens wearers versus in search funds from CooperVi- lution has yet to be found.
spectacle-wearing young people.
sion and B&L, and has a There is particular interest in the Early studies found that progres- proprietary interest in Spe-cialEyes and Alternative Vi- correction of myopia in young people sive addition spectacle lenses and both sion Solutions.
soon after its diagnosis to improve PMMA and conventional GP contact Dr. Bennett is an associate quality of life. About 15 percent of lenses did result in some effect on the professor of optometry at the children become myopic between the progression of myopia (Morrison, University of Missouri-St.
ages of 6-to-14 years, with vision cor- 1960; Stone, 1976; Perrigin et al, Louis and is executive direc- rection often necessary between 8-to- 1990; Khoo et al, 1999; Walline et al, tor of the GP Lens Institute.
10 years of age.
2004). However, all of these studies Dr. DeKinder is an assistant The more important question for failed to find a clinically meaningful clinical professor at the Uni- young people and their parents is: slowing of eye growth.
versity of Missouri-St. LouisCollege of Optometry.
how can the growth of myopia be More recent studies have demon- slowed down? Estimates indicate that strated very little difference between slowing the progression of myopia in myopia increase in GP wearers versus 10_09 SMART_3:Layout 1 9/23/09 12:52 AM Page 25 spectacle-wearing and soft contact lens-wearing tant question pertains to how much myopia is re- young people. In the Contact Lens and Myopia Pro- duced with overnight retainer wear of ortho-k lenses gression (CLAMP) Study (Walline et al, 2004), al- and what improvement results in unaided visual acu- though a greater increase in myopic refractive error ity. The first studies to assess overnight ortho-k were occurred in the soft contact lens control group over a limited to adult ( 18 years of age) subjects. The av- three-year period, much of this difference was attrib- erage amount of myopia reduction ranged from uted to corneal flattening from GP lens wear during –1.76D to –3.33D, with the average final unaided the first year of the study.
acuity approximating No difference in AL pro- 20/20 (6/6) (Swarbrick, The frequency of microbial
gression was noted be- 2006). The amount of av- tween the two groups.
erage myopia reduction is keratitis with a large
A More Promising Op-
somewhat misleading, tion One corrective treat-
subject population over a however; if the higher
ment modality that has myopia subjects (i.e., exhibited great potential five-year period will be
–2.75 to –4.50D) are sepa- in myopia management is rated from the lower my- important to determine.
orthokeratology, also opia subjects (i.e., known as corneal reshap- <–2.75D), then the aver- ing. In the last 20 years, this modality has experi- age refractive error reduction is greater than –3.50D.
enced a rebirth due to the introduction of reverse It is evident that much of the recent research in geometry lens designs, which incorporate a steep re- ortho-k has focused on young people, notably in the verse curve adjacent to the base curve radius as well 8-to-15 age group. This age group in particular may as one-to-two alignment curves located between the derive several potential benefits from overnight or- reverse curve and a peripheral curve.
tho-k. Children of this age are very active and would Recent surveys of contact lens prescribing habits benefit from not wearing spectacles or contact lenses have confirmed the increasing influence of orthoker- for their athletic activities. Certainly the quality of atology. Although worldwide the use of GP lenses is life achieved from not wearing a correction during decreasing, estimated at 9 percent of fits in 2008, or- waking hours would be improved relative to depend- tho-k fits are approximately 1 percent of new fits or ing upon spectacles or contact lenses for correction.
11 percent of all GP fits.
Several recent studies focused exclusively on Patient satisfaction with ortho-k has been con- young people have concluded that ortho-k has great firmed through several quality of life survey studies.
promise as an effective method of myopia control.
Ritchey et al (2005) found not only similar quality of Also, the effects of ortho-k occur at a faster rate with life responses in most categories for ortho-k versus young people than with adults. More important has 30-day continuous wear silicone hydrogel lens wear, been the effect on myopia progression as evidenced but also that the unaided high- and low-con-trast vision of the ortho-k group was similar to the aided vision of the continuous wear group.
Entrance Correction Methods at Enrollment
For subjects wearing both daily wear dispos-able soft lenses and ortho-k, although the soft SOFT LENS
lens wearers achieved better visual acuity andless glare, slightly more than two-thirds (67.7 percent) preferred ortho-k at the conclusion of the study. These studies found that ortho-ksubjects had fewer limitations on daily activi-ties, reduced dependence on correction, and less by changes in AL and vitreous chamber depth lens-related symptoms. Also using a quality of life (VCD). Cho et al (2005) found an approximate survey, Rah et al (2004) found no difference in re- twofold increase for spectacle wearers versus for or- sults between overnight ortho-k and refractive tho-k wearers in both AL (0.29mm for ortho-k ver- surgery patients. This included comparing their per- sus 0.54mm for the spectacle-wearing control group) ceptions about vision, activity limitations, depen- and VCD (0.23mm for the ortho-k group versus dence on correction, and satisfaction with correction.
0.48mm for the control group) over a two-year peri- Studying Ortho-k Effectiveness The most impor-
od for young people between the ages of 7 years and 10_09 SMART_3:Layout 1 9/23/09 12:52 AM Page 26 12 years. Walline (2007) confirmed these results with error change with lens removal, and limited study the first-year results of the Corneal Reshaping and duration. The latter is particularly notable as the Yearly Observation of Nearsightedness (CRAYON) aforementioned studies had a duration of six-to-24 study in which daily wear of both conventional GP months, which is likely an insufficient time period to lenses and soft lenses resulted in an AL increase of monitor long-term AL and VCD growth as well as 0.35mm whereas ortho-k wear resulted in AL such factors as stability of refractive error change, growth of only 0.15mm.
dropout rates, and complications.
However, these clinical studies have suffered from certain limitations including one or more of the fol- lowing: small sample size, high dropout rate, very lit- The aforementioned study limitations resulted in the tle — if any — evaluation of regression of refractive development of the Stabilizing Myopia by Accelerat- ing Reshaping Technique (SMART)study. The intent of the SMART in- Cycloplegic Refractions: D1 and D2 represent two vestigation is to determine whether orthogonal Jackson cross-cyl axes; D3 is the spherical wearing corneal reshaping lenses on an overnight basis stops or slows the pro-gression of myopia in children. The objective of this multicenter investiga- tional protocol is to explore the my-opia stabilization effects of wearing reverse geometry contact lenses and compare them to the controls (wearingdaily wear soft contact lenses) as mea- sured by change in refraction, AL, and VCD. This analysis aims to document anatomical changes that may be associ- ated with increases in myopia as mea- sured by AL and VCD, topography, endothelial cell count, intraocular pressure, and corneal thickness. Dur- ing the five-year study follow-up peri-od, this investigation will also comparethe subjective aspects of vision and Manifest Refractions: D1 and D2 represent two comfort between GP reverse geometry orthogonal Jackson cross-cyl axes; D3 is the spherical contact lens wearers and soft dispos-able contact lens wearers. This will be the first at large examination investi- gating the outcome analysis of acorneal reshaping technique. The remainder of this article will review the protocol and goals of theSMART study.
Study Enrollment and Locations
study is being conducted in accordance with the guidelines provided by the Declaration of Helsinki and in adher- ence to the guidelines of the respective institutions conducting this study. The investigators/investigational sites in- clude the following: Robert Davis, Figure 1. Baseline statistics for cycloplegic and manifest refraction.
OD, FAAO (Davis Eye Care Associ- 10_09 SMART_3:Layout 1 9/23/09 12:53 AM Page 27 ates, Oak Lawn, Ill.), and S. BarryEiden, OD, FAAO (North Subur- Horizontal and vertical K readings ban Vision Consultant, Ltd., Deerfield, Ill.) as co-principal in- vestigators; Michael Lipson, OD,FAAO (University of Michigan Department of Ophthalmology and Visual Sciences, East Lansing, Mich.); Bruce Koffler, MD (Lex- ington, Ky.); Lisa Wohl, MD (Bloomingdale, Ill.), Edward Ben- nett, OD, MSEd, FAAO (St.
Louis, Mo.); P. Douglas Becherer, OD, FAAO (Belleville, Ill.); Robert Gerowitz, OD, FAAO(Palatine, Ill.); Cary Herzberg, Figure 2. Baseline statistics for horizontal and vertical corneal curvature.
OD, FAAO (Aurora, Ill.); andLaMar Zigler, OD, FAAO(Columbus, Ohio).
The study includes 162 treat- Vitreous Chamber Depth (VDpth) ment subjects (80 female, 82 male) fitted by the aforementioned 10investigational sites to determine a reliable outcome analysis for pa- tients fitted with the Boston XO(Bausch & Lomb) GP contact lens polymer in an ortho-k fitting phi- losophy (Emerald Contact Lens Vitreous Chamber Depth (mm) for Overnight Orthokeratology, Euclid Systems Corporation). The net effect of this contact lens fit- ting philosophy is to change thecorneal shape for the sole purpose of reducing the amount of myopia measured by conventional meth-ods. One-hundred-and-five sub-jects (65 female, 40 male) serve as Axial Length (Ax Lgth) controls. These individuals werefitted with the PureVision (Bausch & Lomb) lens worn for daily wearuse and monthly replacement.
The treatment group has a mean age of 11.1 years (rangingfrom 7-to-14 years); the control group has a mean age of 11.7 years Axial Length (mm) (ranging from 7-to-15 years).
Table 1 shows the entrance cor-rection methods of the experimen- Control Ax Lgth OD tal and control groups at Control Ax Lgth OS enrollment into the study. Figure Ortho-K Ax Lgth OD 1 shows baseline manifest and cy- Ortho-K Ax Lgth OS cloplegic refraction of the test andcontrol groups, while Figure 2 Figure 3. Baseline statistics for vitreous chamber depth and axial length.
10_09 SMART_3:Layout 1 9/23/09 12:53 AM Page 28 shows corneal curvature, Figure 3 shows AL and opia, oculomotor nerve palsies, corneal disease, etc.) VCD, and Figure 4 shows pachymetry.
that may affect vision or contact lens wear. Subjects Subject Selection (Inclusion/Exclusion Criteria)
must have normal healthy eyes with no evidence of The investigators selected potential candidates with- lid infection or structural abnormality; a conjunctiva out any requirements as to sex or occupation of the free of infection; a cornea clear and free of edema, subjects or racial/ethnic/religious backgrounds. Sub- scars, staining, vascularization, infiltrates, or opaci- jects currently undergoing ortho-k or subjects previ- ties when examined by slit lamp biomicroscopy; and no evidence of iritis or uveitis(slit lamp findings of grade 0 or 1 could be admitted into theinvestigational study).
6. Systemic health: must be free of systemic disease that may affect vision or vision de-velopment (e.g., diabetes, Down syndrome, etc.). Sub- jects must have no history of allergies that would con- traindicate solution use and/or "normal" contact lens wear.
7. Prescription and specta- cles: subjects must have natu- rally occurring refractive myopia (range as listed previ- ously) and refractive astigma- tism (as listed previously) asdetermined by manifest refrac- Figure 4. Baseline statistics for pachymetry.
tion. The subjects must bewearing a single vision specta- ously successful or unsuccessful in daily or overnight cle lens or no spectacle lens at all at the time of the ortho-k were not eligible for the study.
baseline visit.
8. Medications: subjects must not be taking or 1. Refractive error, non-cycloplegic refraction: must not anticipate taking drugs that might alter sphere powers from –0.75D to –5.00D, inclusive; normal ocular physiology (e.g., eye drops containing cylinder powers up to –2.00DC in axes of 180 de- ephedrine, phenylephrine, etc.), thereby affecting or grees ±20 degrees, all other axes up to –1.00DC.
interfering with successful contact lens wear.
2. Age: male or female subjects 7-to-14 years in- 9. Office visits: subjects must be willing to attend clusive at baseline pre-treatment examination.
all scheduled office visits for the duration of the in- 3. Contact lenses: subjects with previous or cur- rent contact lens wear could be included into the in- vestigational study as long as they discontinued lens 1. Individuals participating in other clinical stud- wear for a minimum of one month before the study.
Subjects must exhibit refractive stability, confirmed 2. Individuals who have clinical signs of kerato- by clinical records. If subjects wore rigid contact conus or other corneal abnormalities.
lenses, two central keratometry readings should not 3. Individuals who are taking or who plan to take have differed by more than –0.50D in either meridi- medication that may cause dry eye (e.g., Accutane) or an. The mires should be regular. No previous ortho- affect vision, corneal curvature, or healing (e.g., cor- keratology patient could be admitted into the 4. Individuals who have undergone intraocular or 4. Visual acuity: 20/25 or better, best-corrected in corneal surgery of any kind.
5. Individuals who have an allergy to any ingredi- 5. Ocular health: must be free of eye disease and ent in the study lens care solutions.
binocular vision problems (e.g., strabismus, ambly- 6. Individuals who have corneas that demonstrate 10_09 SMART_3:Layout 1 9/23/09 12:54 AM Page 30 unstable central keratometry, irregular mires, or that c. Intraocular pressure (annually) show irregular corneal topography.
7. Females who were pregnant, breastfeeding, or 5. Endothelium cell count with specular mi- who intended to become pregnant over the course of croscopy: selected sites (Davis and Becherer) 6. Contact lens comfort, handling, and wearing 8. Individuals who do not meet the inclusion cri- time questionnaire 7. A-Scan measurements (AL, VCD) 9. Individuals who have any ocular structural ab- With treatment subjects, once a year the lenses normality or latent disease (e.g., herpes keratitis) that will be removed and refractive, A-Scan, and kerato- would contraindicate "normal" lens wear. metric/topographic readings will be analyzed for sta-bilization and progression. At yearly intervals, eachsubject will return their treatment lenses to the in- The SMART study should
vestigator to be replaced with soft lenses. Subjectswill be monitored by refraction, topography, A-Scan, help determine the safety
pachymetry, and keratometric readings every three level of overnight ortho-k
days post discontinuation of ortho-k lens wear untiltwo consecutive visits exhibit stabilized readings.
lens wear among young
The investigators will compare the readings to base-line to illustrate the net effect of the treatment pro- people in the United States.
cedure. After the data have been collected, patientswill resume treatment in a new lens with the same Examination Procedures The investigators ex-
specifications as the lens that was returned to the in- amined subjects for eligibility at the baseline exami- vestigator. This procedure will continue each year nation. Subject data was collected at the initial visit that subjects are enrolled into the study.
and will likewise be collected at all follow-up visits.
The same data was collected with the control At the dispensing visit, treatment subjects were given group. At yearly visits the control group is moni- their contact lenses and taught how to apply, re- tored by refraction, topography, A-Scan, pachyme- move, and care for their lenses. The day after the try, and keratometric readings. The readings will be first night of contact lens wear, investigators exam- compared to baseline to illustrate the net effect of ined the treatment subjects within one hour of wak- the control group. ing. At one week, two weeks, one month, three If uncorrected vision was reduced during the ini- months, six months, one year and every six months tial treatment period, disposable soft contact lenses thereafter, the treatment subjects were/will be evalu- were provided or the investigational product was ated, at minimum, eight hours after lens removal.
worn during daytime hours until adequate vision was Control subjects are evaluated following a minimum achieved. This may have been necessary during the of four hours of lens wear. Both the test and control initial two-to-three weeks of the study while the groups will be monitored for refractive changes at treatment effect was stabilizing. Wear of soft contact each visit. If a prescription change is discovered, the lenses was temporary and used only when necessary.
lens power change is provided. Investigators provided Boston Conditioning Solu- Investigators are evaluating each subject for up to tion and Boston Cleaner (both Bausch & Lomb) to a five-year period. The timetable of patient visits was all treatment subjects in this study. If subjects show initiated after the investigator acknowledged that the clinical signs or symptoms of solution allergies, an lens specifications were appropriate. Each examina- alternate solution regimen such as Optimum CDS tion consists of the following procedures: Cleaning, Disinfecting and Storage Solution and 1. Visual acuity (VA) Bailey-Lovie low- and high- Optimum CDS Extra Strength Cleaner (both Lobob contrast acuity charts: total letter count and test dis- Laboratories) will be dispensed. All control subjects tance recorded on the case report form were dispensed ReNu MultiPlus (B&L).
2. Corneal topography3. Refraction (manifest at each visit and cyclo- Preliminary Fitting Results for the Ortho-k
Study Lenses
4. Slit lamp examination Of the 10 investigational sites, only two had previous a. Dilated fundus examination (annually) experience in fitting Euclid Emerald corneal reshap- b. Pachymetry (semi-annually) ing contact lenses. The only data investigators pro- 10_09 SMART_3:Layout 1 9/23/09 12:54 AM Page 31 vided to Euclid to design the initial corneal reshap- strong argument for the ease of fit as well as the level ing lenses was manifest refraction, keratometric data, of patient satisfaction that is obtainable with this and corneal diameter. Based on this information the initial success of fitting was remarkably high. Asshown in Table 2, 80.5 percent of eyes fit into ortho- k were successfully fit with the first lens. Further- It is evident that interest in overnight ortho-k for more, 95.5 percent of orthokeratology-wearing eyes young people is growing based upon the numerous were successfully fit with, at most, one lens change.
clinical studies performed in recent years. However, Success was defined as patient satisfaction with the these studies have only evaluated subjects over a pe- lens and 20/25 or better unaided visual acuity.
riod of no more than two years and often for only sixmonths or less. In addition, the need for a large mul- ticenter longitudinal study that evaluates eye growth, The importance of the SMART study is, in part, its effects of regression over time, ocular health, and longitudinal nature. Evaluating young people over corneal thickness change is very evident. The this long of a time period allows for assessment of SMART study has the potential to be a definitive such factors as regression over time, AL and VCD study on the safety and efficacy of overnight ortho- change, rate of contact lens loss, dropout rates, keratology and the ability of this treatment modality corneal thickness change, endothelial cell change, to control myopia progression. CLS
and adverse events, and the results can be compared The authors would like to acknowledge Bausch & with those of a control group of individuals wearing Lomb for sponsoring the study, Euclid Systems Corpora- a contemporary silicone hydrogel contact lens mate- tion for providing lenses used in this study, and informa- rial. Therefore, the investigators can assess the effect tion provided by Natalie Cogswell, the SMART Study of myopia stabilization with overnight corneal re- coordinator, and Caroline Blackie, the SMART Study shaping on an annual basis through the five-year length of the study. To obtain references for this article, please visit The assessment of long-term adverse events is es- http://www.clspectrum.com/references.asp and click on pecially important. In particular, the frequency of document #167. microbial keratitis with a large sub-ject population over a five-year time period will be important to deter- Statistics on Empirical Fitting With Emerald Lens
mine. The SMART study shouldhelp determine the safety level of NUMBER OF
overnight orthokeratology lens wear TWO LENSES THREE LENSES
among young people in the UnitedStates. The introduction of four- and five-zone reverse geometry ortho-k contact lens designs in the 1990s hasalso resulted in the likelihood that patients can achieve success with their first pair of contact lenses as opposed to reducing myopia to a de- sired level via a series of progressive-ly flatter lenses. Chan et al (2008) reported a first-fit ortho-k success rate of 73.5 percent, with 16 percent requiring two pairs for a successful fit and 7.4 percent needing threepairs. With the large subject sample 253 eyes fit with first lens (314-61) = 80.5%
in the SMART study, obtaining 47 eyes required 1 lens change (2 lenses) 15.0%
more than 80 percent first-fit suc- 12 eyes required 2 lens changes (3 lenses) 4.0%
cess and more than 95 percent with 2 eyes required 3 lens changes (4 lenses) 0.5%
up to one exchange could make a

Source: http://www.emeraldlens.co.kr/wizboard/download.php?filename=Myopia%20Control%20Study(%BF%B5%B9%AEPDF).pdf&UID=26&BID=board02&GID=root

Appendix k: guidelines for treating bipolar disorder

Appendix K: Michigan Implementation of Medication Algorithms (MIMA) Guidelines for Treating Bipolar Disorder MIMA Physician Procedural Manual Appendix K: MIMA Guidelines for Treating Bipolar Disorder Appendix K: MIMA Guidelines for Treating Bipolar Disorder Michigan Implementation of Medication Algorithms (MIMA) Guidelines for Treating


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