Screening for myopic peripheral retinal changes (MPRCs) can be performed in certain situations by a dilated fundus examination (DFE).1,2 The current policy of the Israel Defense Forces (IDF) Medical Corps, which was formulated by a council of board-certified ophthalmologists, is to perform a DFE for all recruits with a myopic spherical equivalent (SE) refractive error (RE) of at least −4.0 diopters (D) in at least one eye. The main rational for this is to rule out severe retinal findings such as retinal tears or retinal holes, which can be prophylactically treated by laser to prevent retinal detachment.3,4 The screening process may reveal — mainly among high myopes — retinal changes, which require follow-up such as cystoid degeneration and “cobble stones,” as well as lattice-like degeneration, meridional folds, enclosed ora bays, retinal pigment epithelial hyperplasia/hypertrophy, and atrophic retinal holes.5–7 Findings of severe peripheral retinal changes in myopic subjects are very rare.8 Of note, MPRCs are positively associated with greater axial length and higher SE.9–11
This is especially correct for mild myopes yielding a low specificity and an unnecessary financial expenditure as well as non-optimal utilization of trained personnel. The goal of this study was to find the optimal degree of myopic RE that justifies screening on a national scale. This, in turn, may serve as a recommendation for evidence-based screening policy.12
The aim of this study was to identify the lowest SE RE for best effective screening of myopic enlisted subjects following the IDF medical policy to rule out peripheral retinal changes necessitating prophylactic laser retinopexy.
Patients and Methods
The Israeli National Military Service Act requires all 17-year-old Israelis to present themselves to a local IDF recruitment center. At the end of an extensive medical evaluation process, a medical profile and appropriate Functional Classifications Codes (FCCs) are assigned to each recruit and stored in a computerized database. FCCs describe the medical and mental status (condition and severity, as well as an element of occupation) and are similar to the International Classification of Diseases (ICD) coding. The law and the populations that are exempt from service, as well as the medical process and its outcomes, were previously described in detail.13–15
The computerized database of the northern recruitment center of Israel was used for this study, previously shown to have a stringent, high-quality medical process and reliable medical data.14,15
The study population consisted of consecutive candidates for recruitment to the IDF who were 15 to 20 years old with myopia and a spherical equivalent of at least −4 D in at least one eye who were born between 1978 and 1994 and completed the medical profiling process between 1998 and 2011.
The Medical Examination
All candidates for recruitment underwent an uncorrected visual acuity test (UCVA) making use of a Snellen chart. The test was carried out by professional technicians who were trained by an ophthalmologist according to protocols that were published by the IDF Medical Corps. Adherence to these protocols and using the same methods throughout the study years were strictly kept.
Candidates who were unable to read more than one letter correctly in the 1.0 (6/6) line underwent an automated non-cycloplegic refraction (Speedy K; Nikon, Tokyo, Japan; or KR-8000 and KR7000S; Topcon, Tokyo, Japan; and earlier models) followed by a subjective refraction examination to determine their best-corrected visual acuity (BCVA) in each eye by a certified optometrist or an ophthalmologist. Further details on the medical examination process were previously provided.16
IDF's Medical Corps regulations dictate a mandatory DFE to all myopic candidates for recruitment with a SE RE of at least −4 D in at least one eye. The DFE was performed by applying one drop of tropicamide 1% in each eye into the inferior fornix twice 5 minutes apart and performing the examination 20 minutes later. After sufficient pupillary dilatation was achieved, the subjects were examined by an indirect ophthalmoscopy (Welch Allyn, Skaneateles Falls, NY) followed by a tri-mirror contact lens (Volk Optical, Mentor, OH) using a slit-lamp (Haag-Streit, Köniz, Switzerland) to achieve the best visualization of the peripheral retina.
During the whole study period, only two ophthalmologists were involved in these medical examinations, yet each subject was examined by one ophthalmologist. Of note, both of these senior ophthalmologists were highly experienced in fundus examination and were skilled in the regulations and FCCs coding. Upon assignment of FCC — MPRC-related as every other FCC — by the examining senior ophthalmologist, it was re-assigned independently by the head physician of the recruitment center, according to the described findings, in order to prevent coding mistakes. The medical examination findings and the FCCs, if assigned, we documented in both the hard copy medical file as well as in the computerized database and were used in this study to estimate MRPC prevalence.12,14
Following the current policy of the IDF medical corps to perform a DFE to all recruits with a myopic SE RE of at least −4.0 D in at least one eye, the inclusion criteria in this study was a SE RE for every subject of the more myopic eye of −4 D or higher. In addition, to control for anisometropia, only subjects with both eyes being myopic (each of −4D or higher) and a difference of up to 1D between myopic eyes were included in this study (Figure 1).
Schematic diagram of the study design. DFE = dilated fundus exam; SE = spherical equivalent; RE = refractive error
The results of the DFE were classified into three categories: normal, mild myopic degenerative peripheral retinal changes, or moderate-to-severe myopic degenerative peripheral retinal changes (Table 1). Mild changes, such as cobble stones or cystoid degenerations, required only follow-up. In contrast, moderate-to-severe changes, such as retinal tears or retinal holes, required prophylactic laser retinopexy consideration of the involved retinal areas. Note that all patients were asymptomatic without previous ophthalmic history of laser retinopexies or surgeries. Symptoms such as floater or flashes were reported to be correlated with the necessity of treatment for atrophic holes within peripheral retinal degenerations.17 However, this information was not part of the computerized database on which this study was based and, hence, could not have been included in the current study neither for judgement of necessity of fundus examination nor as criteria for treatment, etc. Either way, the relation between symptoms and policy is not within the scope of this study.
Definitions and Findings Related to Mild and Moderate-to-Severe MPRCs
The sensitivity of a cutoff of the RE to perform a DFE is calculated by dividing the number of myopic patients with MPRC, who would have been examined with this cutoff by the number of all the myopic subjects with MPRC in this study. The specificity of a cutoff of a RE reflects the number of all myopic subjects with no retinal changes, who would not have been examined with this cutoff divided by the number of all myopic subjects with no retinal changes in this study.
All analyses were carried out using the SPSS statistical package (version 22.0; IBM Corporation, Armonk, NY). Logistic regression analysis was performed to examine the relation between the RE and the chance to have a peripheral retinal change. This resulted in a coefficient of myopia with its P value, odds ratio (OR), and 95% confidence interval (CI). The receiver operating characteristic (ROC) curve is a plot of sensitivity against 1 minus specificity (as defined above) for the different SE cutoff points.18 The value of the Youden index (maximum [sensitivity + specificity − 1]) to yield optimal sensitivity and specificity on the ROC curve was calculated.19 SE cutoff ability to distinguish between good and poor MPRC diagnosis was tested by using area under the curve (AUC).20 A higher value of an AUC (toward 1) represented a better discriminative performance.
This study was approved by an IDF Institutional Review Board (IRB) ethics committee (Approval number: #1199-2012), and it adhered to the tenets of the Declaration of Helsinki.
Of 3,400 myopic subjects who fulfilled the IDF medical corps criterion to DFE referral (SE RE of at least −4.0 D in at least one eye), 2,991 were found to have myopia in the right eye (87.97%), 2,949 were found to have myopia in the left eye (86.74%), and 2,540 (74.71%) were found to have myopia in both eyes. Of these individuals, 254 (10.00%) were excluded as the difference between the myopic eyes was greater than 1 D. The final study population consisted of 2,286 consecutive myopic candidates for recruitment to the IDF which had a SE RE of −4 D or higher in both eyes, and a difference of up to 1D between myopic eyes (Figure 1).
The mean age was 17.50 years ± 0.69 years (range: 15 years to 20 years). Males (1,163) comprised 50.87% of study participants. Of the participants, 1,921 subjects (84.03%) were born in Israel and the remaining 365 subjects (15.97%) were immigrants. The majority (93.13%) of the study population were Jewish.
The average SE RE of the right myopic eye was −5.61 D ± 1.64 D (range: −4.00 D to −21.00 D). The average SE RE of the left myopic eye was −5.62 D ± 1.64 D (range: −4.00 D to −21.00 D). The average BCVA of the right eye was 0.93 ± 0.15 (range: 0.10 to 1.00). The average BCVA of the left eye was 0.94 ± 0.14 (range 0.10 to 1.0). The average SE RE of the more myopic eye, as defined earlier, was −5.76 D ± 1.65 D.
Ninety-five subjects (4.16%) were found to have MPRC. Of these subjects, 93 (97.89%) had mild MPRC and two (2.11%, comprising only 0.09% of the whole study myopic population) had moderate-to-severe MPRC, which may necessitate laser retinopexy of involved retinal areas. The SE RE of subjects with mild MPRC was between −4 D and −18.25 D. The SE RE of subjects with moderate-to-severe MPRC was between −7.5 D and −10.125 D.
The higher the SE RE of the more myopic eye, the higher the prevalence of MPRC among the myopic subjects (Table 2). Of note, within the ranges of −4 D to −15 D, almost a linear relationship was obtained.
Prevalence of MPRC in Myopic Subjects Stratified by SE RE Ranges (D)
Logistic regression analysis was performed to examine the correlation between SE RE and the chance to have MPRC. The estimated coefficient of myopia was −0.347 (P < .0001) with an OR of 0.71 (95% CI, 0.65–0.77). Similar significant findings were obtained when the model included additional demographic variables such as year of birth, gender, immigration status, ethnic origin, age, religion, area of residence, and education.
Sensitivity and specificity were calculated for each SE RE (Table 3, Figure 2) and were plotted against each other (Figure 3). A ROC analysis was performed. The AUC was 0.774 (95% CI, 0.725–0.822; P < .0001). The derived Youden index gave a SE RE of −6.25 D with a sensitivity of 72.63% and a specificity of 73.44%. Utilizing this as the cutoff for DFE would have led to examine only 651 (28.48%) of the 2,286 subjects who were examined when the cutoff was −4 D. Of the 95 subjects with MPRC, only 69 (72.63%) subjects — including these with moderate-to-severe MPRC — would have been examined utilizing this cutoff.
Sensitivity and Specificity of a DFE to Screen for MPRC
A receiver operating characteristic curve of cutoffs to perform a fundus examination to find myopic-related peripheral retinal changes. The cutoffs are the spherical equivalent refractive error of the more myopic eye of the two myopic eyes for each subject.
Sensitivity and specificity versus spherical equivalent refractive error of the more myopic eye of the two myopic eyes for each subject.
A positive relationship was obtained between SE RE and prevalence of MPRC, at least within the range of −4.0 D to −15.0 D (Figure 3). The logistic regression analysis and the AUC of the ROC analysis showed that there is a high correlation (P < .0001) between SE RE and the chance to have MPRC.
Applying the cutoff of a SE RE of −6.25 D as derived by the Youden index, a sensitivity of 72.63% and a specificity of 73.44% were obtained. This could eliminate the need to examine (according to the current criteria) 1,635 subjects (71.52%) who had a SE RE of at least −4.0 D but less than −6.25 D. However, during a 14-year period, this amounts to only approximately 117 DFE performed annually in northern Israel. The two subjects with moderate-to-severe MPRC would still be included in the study population (RE range: −7.5 D to −10.125 D; in agreement with SE RE range of −7.5 D to −13.5 D among 10 myopic subjects who were diagnosed until 1997, where the SE RE cutoff was −6.0 D). Twenty-six subjects with mild MPRC (27.37% of all subjects with MPRC) would not have been examined. However, mild MPRC are practically of low clinical significance.11,21,22
The lowest SE RE in our study population of subjects with moderate-to-severe MPRC was −7.50 D. Using a cutoff SE RE of −7.50 D would have yielded a specificity of 88.04% and a sensitivity of 46.32%. Of the 2,286 subjects having both eyes myopic in our study, only 306 (13.39%) would have been examined, whereas the remaining 1,980 subjects (86.61%) would not have been examined. This is tantamount to 141.5 examinations per year in Northern Israel. On the other hand, 51 subjects with mild MPRC (53.68% of all subjects with MPRC) would not have been examined.
Most armies around the world did not include a fundus examination as part of the routine medical examination of conscripts. It only included visual acuity (VA) testing (in some instances only uncorrected), color vision testing, or examination of the anterior part of the eye.23–25 One study,26 however, stated that people attempting to enlist to the U.S. Army who fail to see 20/20 in each eye with their current spectacles must undergo further ophthalmic examination. It was specifically mentioned that DFE was performed only when there was a high probability of a disqualifying condition. The article did not elaborate about these conditions. Another report described fundus findings of enlisted personal with reduced VA resulting from congenital fundus defects that was present only in the minority of cases.27 Subsequently, asymptomatic subjects in the U.S. military affected with retinal diseases, as well as peripheral retinal degenerative changes, could be missed. A study from the Republic of Korea showed that soldiers were examined solely by conventional vision testing.28 It recommended that a fundus examination and visual field test could be more useful tools for a large-scale draft screening to detect the most common visual impairments that lead to medical retirement from the army. Of note, a significant percentage of medical retirements due to visual impairment resulted from non-traumatic retinal diseases, even though these patients were young. In contrast, DFE to a subset of high myopic conscripts to the IDF is a robust way to detect subjects with moderate to severe MPRC. That was validated by the large population size (2,286 myopic subjects), the long period of data collection (14 years), the robust regulations and methodology, the standardized high-quality medical examination, and stable definition of MPRC; these are all key strengths of the study, which enable to base our conclusions on a solid and valid population wide database.
Nevertheless, there were also certain limitations to this study. The first obvious ones are related to the retrospective nature and cross-sectional design. It was restricted to only one recruitment center (in northern Israel), with an under-representation of certain populations (such as minorities, religious populations, and women who are married, pregnant, or mothers — all of whom are exempt from service by law).13,29 It also follows the current policy of IDF medical corps to perform DFE to all recruits with a SE RE of at least −4.0 D in at least one eye, thus the derived “100% sensitivity” in the study is at −4.0 D. Furthermore, it is not possible to directly link between MPRC to a given eye (either right or left, or even both), and anisometropia — although partially controlled in this study — should be considered while deducing the cutoff. Also, the number of MRPCs in the same eye is not specified in the raw database.
This study has a few potential biases. It reflects screening examinations performed to subjects from a certain geographical area during a specific period in time, thus not necessarily being able to extrapolate the finding to the current age group of teenagers. Secondly, this study pertains to a certain age group and as we know MPRC may increase over time,30–32 therefore not reflecting the medical condition of older subjects. Thirdly, although throughout the entire study period only two highly experienced senior ophthalmologists were involved, each subject was examined by one ophthalmologist; therefore, inter-rater reliability could not have been determined.
DFE has few risks mainly very rare side effects from the cycloplegic agents as well as the occasional corneal stippling or the rare erosion from the somewhat bulky contact tri-mirror lens.33,34 It is considered to be a noninvasive examination.34,35 The cost of the examination is only that of the medical staff fee, which is low compared to a more advanced retinal imaging.1,2,36,37 Based on our findings, a SE cutoff of −6.25 D was shown to provide the highest combined sensitivity and specificity. Therefore, this is the optimal SE cutoff for screening myopic teenagers for MPRC.
Yet, screening of pre-enlistees to obligatory military service would favor sensitivity over specificity. This would fulfill the demand for maximal compatibility between the pre-enlistee's health status and the expected service conditions and requirements. The risk and cost of the examination are low, and trained ophthalmologists — specifically medical retinal experts — are available. Therefore, it hardly poses a low burden of unnecessary DFE on the national health system. Henceforth, we suggest retaining the SE RE cutoff as the current one (−4.0 D) to ensure a highest sensitivity.
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Definitions and Findings Related to Mild and Moderate-to-Severe MPRCs
|Mild MPRC||Moderate-to-Severe MPRC|
|Definition||Requires only follow-up||May require prophylactic laser retinopexy|
|Signs (Description)||Cobble stones (areas of atrophy of the outer retina);38 cystoid degenerations (zones of microcysts);39–41 lattice degenerate (retinal atrophy and irregularity of the inner layers with an overlying pocket of liquefied vitreous, condensation, and adherence of vitreous at the margin of the lesion);42,43 vitreoretinal tufts (small, peripheral, focal area of elevated glial hyperplasia associated with vitreous or zonular attachment and traction);44 meridional folds (folds of redundant retina);31,38 enclosed ora bays (sections of pars plana epithelium located immediately posterior to the ora serrata surrounded by retina);38 peripheral retinal excavations;38 retinal pigment epithelial hyperplasia;41–43 retinal pigment epithelial hypertrophy;41–43 atrophic retinal holes41,45,46||May require prophylactic laser retinopexy;retinal tears (a strip of retina is pulled anteriorly by vitreoretinal traction);41,45,46 retinal operculated holes (a piece of retina is completely free)41,45,46|
|% of MPRC Cases||97.89%||2.11%|
|% of Study Population||4.07%||0.09%|
|Range of Spherical Equivalent Refractive Error of the More Myopic Eye||−4.00 D to −18.25 D||−7.50 D to −10.125 D|
Prevalence of MPRC in Myopic Subjects Stratified by SE RE Ranges (D)
|SE RE Range (D)|
Sensitivity and Specificity of a DFE to Screen for MPRC
|Spherical Equivalent (D)||Sensitivity (%)||Specificity (%)|