Fundus Photography

Number: 0539

Policy

1. Aetna considers fundus photography medically necessary for any of the following indications:

   • Abnormal electro-oculogram (EOG)
   • Abnormal oculomotor studies
   • Abnormal retinal function studies
   • Abnormal visually evoked potential
   • Age-related macular degeneration
   • Benign neoplasm of choroid, cranial nerves, eyeball, or retina
   • Carcinoma in situ of eye
   • Chorioretinal inflammation, scars, and other disorders of choroid
   • Color vision deficiencies
   • Congenital anomalies of posterior segment of eye
   • Congenital glaucoma
   • Congenital rubella
   • Diabetes mellitus (diabetic retinopathy)
   • Disorders of aromatic amino-acid metabolism affecting the fundus
   • Disorders of globe
   • Disorders of optic nerve and visual pathways
   • Endophthalmitis
   • Glaucoma and glaucoma suspects
   • Hamartoses involving the eye
   • Histoplasmosis
   • Human immunodeficiency virus (HIV) disease
   • Initial baseline evaluation and periodical follow-up of individuals being treated with ethambutol (Myambutol)
   • Lupus erythematosus
   • Malignant neoplasm of eye
   • Monitoring of members for toxicity by anti-malarials such as chloroquine (Aralen), hydroxychloroquine (Plaquenil) and drugs acting on other blood protozoa
   • Multiple sclerosis
   • Penetration of eyeball with magnetic or non-magnetic foreign body
   • Peters anomaly
   • Pseudotumor cerebri
   • Retinal detachment and defects
   • Rheumatoid arthritis and other inflammatory polyarthropathies
   • Sickle-cell anemia
   • Syphilitic retrobulbar neuritis
   • Systemic lupus erythematosus
   • Toxoplasmosis
   • Tuberous sclerosis
   • Other retinal disorders where the results of fundus photography will change the treatment of the member.

2. Frequency of Testing:

   Aetna considers fundus photography medically necessary no more than two times per year. Justification for more frequent testing must be documented in the medical record.

3. Aetna considers fundus photography experimental and investigational for screening in asymptomatic persons without signs or symptoms of disease and for all other indications (e.g., evaluation of neurofibromatosis type 1, non-penetrating traumatic eye injury, pigment dispersion syndrome, tamoxifen use, and toxocariasis) because there is insufficient evidence that this test affects management for these other indications such that clinical outcomes are improved.

   Note: Fundus photography of a normal retina is considered not medically necessary.

4. Aetna considers computer-aided animation and analysis of time series retinal images (e.g., MatchedFlicker) experimental and investigational for monitoring disease progression and for all other indications.

5. Aetna considers automated color fundus photography for detection and screening of age-related macular degeneration experimental and investigational because the effectiveness of this approach has not been established.

Background

Fundus photography involves the use of a retinal camera to photograph the regions of the vitreous, retina, choroid, and optic nerve.  The resultant images may be either photographic or digital and become part of the member's medical record.  Fundus photographs are usually taken through a dilated pupil in order to enhance the quality of the photographic record, unless unnecessary for image acquisition or clinically contraindicated.

Fundus photography is indicated to document abnormalities related to disease processes affecting the eye or to follow the progress of the disease, and is considered medically necessary for such conditions such as macular degeneration, retinal neoplasms, choroid disturbances and diabetic retinopathy, or to identify glaucoma, multiple sclerosis, and other central nervous system abnormalities.

Fundus photographs are only considered medically necessary where the results may influence the management of the patient.  In general, fundus photography is performed to evaluate abnormalities in the fundus, follow the progress of a disease, plan the treatment for a disease, and assess the therapeutic effect of recent surgery (e.g., photocoagulation).  Fundus photographs are not medically necessary simply to document the existence of a condition.  However, photographs may be medically necessary to establish a baseline to judge later whether a disease is progressive.

A CGS Administrators, LLC Medicare Local Coverage Determination (LCD) allows coverage of fundus photography (L34399) for diagnosis of conditions such as macular degeneration. Fundus photography is usually medically necessary no more than two times per year. Fundus photography of a normal retina will be considered not medically necessary.

A First Coast Service Options, Inc. Medicare Local Coverage Determination (LCD) also allows coverage of fundus photography (L33670) and states that “fundus photos may be of value in the documentation of rapidly evolving diabetic retinopathy. In the absence of prior treatment, studies would not generally be performed for this indication more frequently than every 6 months.”

A National Government Services, Inc. Medicare Local Coverage Determination (LCD) allows coverage of fundus photography (L33567) which states that “fundus photography may be used for the diagnosis of conditions such as macular degeneration, retinal neoplasms, choroid disturbances and diabetic retinopathy, glaucoma, multiple sclerosis or other central nervous system anomalies.” It is not covered if study is performed as a “screening” service. Fundus photography is usually medically necessary no more than two times per year. Fundus photography of a normal retina will be considered not medically necessary.

Sequential series of photographs are considered medically necessary only if they document a clinically relevant condition that is subject to change in extent, appearance or size, and where such change would directly affect the management.  Repeat fundus photography may be medically necessary when an examination of the fundus reveals that the disease of condition of the fundus has progressed, such that prior fundus photographs no longer depict the pathology at the present time.  Repeated fundus photographs of the same disease or condition, without any meaningful change, are not considered medically necessary.  In addition to disease progression, repeat fundus photographs may be necessary if there is a new disease affecting the fundus, or for planning for additional surgical treatment.  Routine images to embellish the record, but a succession of which would not influence treatment, are not considered medically necessary.  When performed concurrently, the medical necessity of fundus photography and scanning computerized diagnostic imaging of the posterior segment should be documented in the medical record.

Documentation in the patient's medical record should include a current, pertinent history and physical examination, and progress notes describing and supporting the covered indication for fundus photography, and pertinent prior diagnostic testing and completed report(s), including, when appropriate, previous fundus photographs.  Fundus photographs should be properly labeled as to which eye they represent, the date they were taken, and the date they were reviewed.  The medical records should document the findings of the fundus photography, including a description of changes from prior fundus photographs (if any), and an interpretation of those findings, and the implications of the photographic evidence, including whether any chages in the treatment plan will be instituted as a result of the photographs.  Fundus photographs without an interpretation are considered not medically necessary.  All documentation must be maintained in the member’s medical record.  The record must be legible and include appropriate patient identification information (e.g., complete name, dates of service(s)), as well as the physician or non-physician practitioner responsible for and providing the care of the patient.

When indicated for glaucoma, the interpretation of the fundus photographs should include a report of the vertical and horizontal cup/disc ratio based upon vessel pattern and/or coloration, the presence or absence of diffuse or focal pallor, the presence or absence of asymmetry, and the presence or absence of progression regarding any of the above parameters.  If the fundus photographs include red-free images, commentary on the status of the retinal nerve fiber layer should accompany the images.

The American Academy of Ophthalmology (Marmor et al, 2011) does not recommend the use of fundus photography for screening of chloroquine and hydroxychloroquine retinopathy.  It is not sensitive enough for screening because recognizable bull's-eye retinopathy signifies relatively advanced chloroquine or hydroxychloroquine toxicity.

Salcone et al (2010) stated that retinopathy of prematurity (ROP) is a vision-threatening vaso-proliferative condition of premature infants worldwide.  As survival rates of younger and smaller infants improve, more babies are at risk for the development of ROP and blindness.  Meanwhile, fewer ophthalmologists are available for bedside indirect ophthalmoscopy screening examinations.  Remote digital imaging is a promising method with which to identify those infants with treatment-requiring or referral-warranted ROP quickly and accurately, and may help circumvent issues regarding the limited availability of ROP screening providers.  The Retcam imaging system is the most common system for fundus photography, with which high-quality photographs can be obtained by trained non-physician personnel and evaluated by a remote expert.  It has been shown to have high reliability and accuracy in detecting referral-warranted ROP, particularly at later post-menstrual ages.  Additionally, the method is generally well-received by parents and is highly cost-effective.

An UpToDate review on "Retinopathy of prematurity" (Paysse, 2012) does not mention the use of digital imaging or fundus photography.  It states that "screening evaluation consists of a comprehensive eye examination performed by an ophthalmologist with expertise in neonatal disorders".

An UpToDate review on “Toxocariasis: visceral and ocular larva migrans” (Weller and Leder, 2013) does NOT mention the use of fundus imaging/photography.

Computer-aided animation and analysis of time series retinal images (e.g., MatchedFlicker) has been proposed for use in monitoring glaucoma and other retinal diseases. According to the manufacturer of the MatchedFlicker (EyeIC, Wayne, PA), the technology automatically aligns and registers two images of the same object taken at different points in time, and generates a superimposed view that is alternated back and forth (i.e., a flicker). In so doing, areas of change present between the two images appear as motion. 

MatchedFlicker has been cleared by the FDA based upon 510(k) premarket notification as a class II device.

The manufacturer states that MatchedFlicker helps to improve both the speed and accuracy of image diagnostic evaluations, resulting in more efficient workflow, more accurate patient diagnosis, and ease of documentation (EyeIC, 2014).

Studies have compared computer-aided animation and analysis of time series retinal images to side-by-side comparison of photographic images in a number of retinal diseases, including detection of glaucoma and screening of premature infant eyes for retinopathy of prematurity. Clinical utility studies are ongoing.

Screening for Diabetic Retinopathy

van Ballegooie and van Everdingen (2000) stated that early detection and adequate treatment of complications of diabetes mellitus (DM) are important for many patients in maintaining independence and ability to work. Diabetic retinopathy (DR) cannot be prevented.  Limitation of damage is possible by aiming for normoglycemia and normotension.  While exudative as well as proliferative retinopathy can occur without any visual symptom, regular ophthalmological examination is necessary for timely laser coagulation.  Fundus photography for screening is applicable under certain conditions; fluorescence angiography can be useful in patients with understood deterioration of visual acuity or diabetic maculopathy.  In many patients foot disease can be prevented by simple measures: examining the foot at least once-yearly, recognition of the foot with a high level of risk, education of patient and family, adapted shoes and preventive foot care.  Treatment of a foot ulcer consists of relief of mechanical pressure, repair of disturbed skin circulation, treatment of infection and edema, optimal metabolic control, frequent local wound care and education.  Patients with a diabetic foot have to be thoroughly followed-up for the rest of their lives.  For patients with diabetic nephropathy cardiovascular complications are the main causes of morbidity and mortality.  Of all patient with DM older than 10 years, urine has to be examined for loss of albumin at least once-yearly.  Treatment of nephropathy consists of non-smoking, sufficient physical exercise, reduction of over-weight, well-composed nutrition and particularly treatment of hypertension.  Diagnosing cardiovascular diseases in patients with DM is in principle the same as for other patients.  Treatment of hyper-cholesterolemia has to be based on an absolute risk of 20 % for cardiovascular disease in the following 10 years.  The limit for treatment will be reached earlier in the presence of micro-albuminuria, persistent high HbA1c greater than 8.5 %, triglyceride concentration greater than 2.0 mmol/L, or a positive family history with myocardial infarction less than 60 years.  In proven cardiovascular disease one needs to strive for optimization of the glucose metabolism, non-smoking and if necessary drug therapy.

Massin et al (2003) compared the results of fundus photography using a new non-mydriatic digital camera with the results of reference standard of Early Treatment Diabetic Retinopathy Study (ETDRS) retinal photographs, for the detection of DR. Fundus color photographs were taken with a Topcon non-mydriatic camera of 147 eyes of 74 diabetic patients, without pupillary dilation (5 overlapping fields of 45 degrees; posterior pole, nasal, temporal, superior and inferior).  Three retinal specialists classified the photographs in a masked fashion, as showing no DR or mild non-proliferative DR (NPDR) not requiring referral, moderate or more severe NPDR and/or macular edema, or as non-gradable image requiring referral; ETDRS 35-mm color slides served as reference images for DR detection.  For moderately severe to severe DR, the sensitivities of detection reported by the 3 observers were 92, 100 and 92 %, respectively, and the specificities, 87, 85, and 88 %, respectively.  For 4 levels of DR severity (none or mild NPDR, moderate NPDR, severe NPDR and proliferative DR), the percentages of exact agreement between the 3 observers on the retinopathy grades assigned to the non-mydriatic photographs and to the ETDRS reference slides were 94.6, 93 and 87.6 %, respectively (kappa 0.60 to 0.80); 16 eyes of 9 patients (11%) were judged un-gradable by at least 1 observer.  In a second series of 110 patients, evaluated in the setting of a screening procedure, fewer photographs were un-gradable (less than 6 %).  The authors concluded that these findings suggested that fundus photographs taken by the Topcon TRC-NW6S non-mydriatic camera, without pupillary dilation, are suitable for DR screening. 

Polak and colleagues (2008) noted that the revised evidence-based guideline “Diabetic retinopathy: Screening, diagnosis and treatment” contained important recommendations concerning screening, diagnosis and treatment of DR. Regular screening and the treatment of risk factors, such as hyperglycemia, hypertension, obesity and dyslipidemia, can prevent retinopathy and slow down its development.  Fundus photography is recommended as a screening method.  If necessary, diagnosis by biomicroscopy and a treatment consisting of photocoagulation and/or vitrectomy should be performed by the ophthalmologist.  The re-assessment of responsibilities is a vital component of the implementation of the guideline bearing in mind that the screening in particular, can be performed by personnel other than ophthalmologists.

In a cross-sectional study, Germain and associates (2011) compared the efficiency of the DR screening with digital camera by endocrinologists with that by specialist and resident ophthalmologists in terms of sensitivity, specificity, and level of "loss of chance". A total of 500 adult diabetic patients (1,000 eyes) underwent 3-field retinal photography with a digital fundus camera following pupillary dilatation; 5 endocrinologists and 2 ophthalmology residents underwent 40 hours of training on screening and grading of DR and detection of associated retinal findings.  A κ test compared the accuracy of endocrinologist and ophthalmology resident screening with that performed by experienced ophthalmologists.  Screening efficiency of endocrinologists was evaluated in terms of "loss of chance", namely, missed diagnoses that required ophthalmologist referrals.  The mean weighted κ of DR screening performed by endocrinologists was similar to that of ophthalmology residents (0.65 versus 0.73).  Out of 456 DR eyes, both endocrinologists and ophthalmology residents mis-diagnosed only stage 1 DR (36 and 14, respectively), which did not require ophthalmologist referral.  There were no significant differences between endocrinologists and ophthalmology residents in terms of diabetic maculopathy and incidental findings except for papillary cupping and choroidal lesions, which were not the main purpose of the study or of the training.  The authors concluded that endocrinologist with specific training for DR detection using a 3-field digital fundus camera with pupillary dilatation could perform a reliable DR screening without any loss of chance for the patients when compared with identical evaluation performed by experienced ophthalmologists.

Guigui et al (2012) reviewed the current screening methods for DR, with a focus on non-mydriatic digital fundus photography. Articles from Medline were reviewed from 1976 to November 2011 for different combinations of the words "diabetic retinopathy", "screening", "fundus photography" and "nonmydriasis".  Current research has proven that pupillary dilation is not a necessary step in the fundus examination, although it reduces the number of unnecessary referrals to ophthalmologists.  Automated grading systems, while saving time and reducing human error, still need refinement before they can replace manual grading by trained ophthalmologists.  The authors concluded that non-mydriatic digital fundus photography with manual grading by a trained technician is an acceptable method of screening for DR.

Ku and colleagues (2013) evaluated the accuracy of grading DR using single-field digital fundus photography compared with clinical grading from a dilated slit-lamp fundus examination in Indigenous Australians living in Central Australia. Main outcome measures included sensitivity and specificity of grading using digital photography compared with the clinical gold standard of slit-lamp fundus examination.  Of the 1,884 participants recruited for the study, 1,040 had self-reported DM and, of those, 360 had fundus photographs available (706 eyes) that were able to be graded.  On clinical grading, 163 eyes had any DR and 51 eyes had vision-threatening DR (VTDR).  The sensitivity and specificity for detecting any DR were 74 % (95 % confidence interval [CI]: 67 % to 80 %) and 92 % (95 % CI: 90 % to 94 %), respectively.  The sensitivity and specificity for detecting VTDR were 86 % (95 % CI: 77 % to 96 %) and 95 % (95 % CI: 93 % to 97 %), respectively.  The authors concluded that single-field digital fundus photography is a valid screening tool for DR in remote communities of central Australia and may be used to provide eye care services to this region with acceptable accuracy.

An UpToDate review on “Diabetic retinopathy: Screening” (McCulloch, 2016) states that “Ophthalmoscopy is a reasonable screening method when performed by well-trained personnel on dilated fundi. The accuracy of ophthalmoscopy is substantially lower when performed by primary care physicians.  As an alternative, 7-field stereoscopic fundus photography is another acceptable method, but also requires both a trained photographer and a trained reader.  Fundal photography compares favorably with ophthalmoscopy (performed by an experienced ophthalmologist, optometrist, and ophthalmic technician) …. In patients with diabetes, we recommend screening for diabetic retinopathy (DR) (Grade 1B).  Screening must be performed by those with expertise and can be accomplished with dilated fundus examination or retinal photography”.

Diagnosis and Management of Diabetic Retinopathy

The Institute for Clinical Systems Improvement’s clinical practice guideline on “Diagnosis and management of type 2 diabetes mellitus in adults” (Redmon et al, 2014) stated that “A dilated eye examination for diabetic eye disease performed by an ophthalmologist or optometrist is recommended annually for patients with T2DM. Less frequent exams (every 2 to 3 years) may be considered in the setting of a normal eye exam.  The role of fundus photography is still being considered but doesn't replace a comprehensive exam”.

Monitoring of Ethambutol-Induced Optic Neuropathy

Chung and associates (1989) reported the case of a 54-year old Chinese woman with miliary choroidal tuberculosis who was followed for more than 3 years.  She had had tuberculous meningitis for about 1 month before an ophthalmologic examination for blurred vision OU (oculus uterque meaning both eyes).  There were 50 to 60 choroidal tubercles OU which were located mostly at the posterior poles including the macular areas.  The meningitis and tubercular lesions resolved with anti-tuberculous medications.  In a series of fundus photographs and fluorescein angiograms, a macular subretinal neovascularization was noted in association with the tubercular lesions, which resulted in disciform maculopathy.  The authors stated that this case had the largest number of tubercles reported in this century, and the association of macular subretinal neovascularization with choroidal tuberculosis has never been reported.

In a prospective, longitudinal, cohort study, Han and colleagues (2015) evaluated longitudinal analysis of peri-papillary retinal nerve fiber layer (RNFL) and peri-foveal ganglion cell-inner plexiform layer (GCIPL) thickness in patients being treated with ethambutol (EMB).  This study enrolled 37 patients who were treated with EMB for pulmonary tuberculosis.  Best-corrected visual acuity (BCVA), color vision test, automated perimetry, fundus photography, and RNFL and GCIPL thickness were measured at baseline and at 4 and 6 months after the start of EMB treatment, using Cirrus optical coherence tomography (OCT).  Among 37 patients, EMB-induced optic neuropathy occurred in 1 patient (2.7 %).  In this patient, thickening of the RFNL and thinning of the GCIPL were noted at the onset of symptoms.  After discontinuation of EMB, RNFL and GCIPL thickness progressively normalized.  Changes in RNFL and GCIPL thickness were not statistically significant in the 36 patients who did not exhibit EMB-induced optic neuropathy-related symptoms during follow-up (all p  > 0.05).  The authors concluded that thickening of the peri-papillary RNFL and thinning of the peri-foveal GCIPL is an effective quantitative and early marker for diagnosis of EMB-induced optic neuropathy.

Furthermore, the American Optometric Association recommends fundus photography for initial baseline evaluation and periodical follow-up of individuals being treated with ethambutol. .

Age-Related Macular Degeneration

The American Academy of Ophthalmology Preferred Practice Pattern on age-related macular degeneration (AAO, 2015) states: "Color fundus photographs may be obtained when angiography is performed, because they are useful in finding landmarks, evaluating serous detachments of the neurosensory retina and RPE, and determining the etiology of blocked fluorescence. Fundus photographs may also be used as a baseline reference for selected patients with advanced non-neovascular AMD and for follow-up of treated patients." 

Holz and colleagues (2017) summarized the results of 2 consensus meetings (Classification of Atrophy Meeting [CAM]) on conventional and advanced imaging modalities used to detect and quantify atrophy due to late-stage non-neovascular and neovascular age-related macular degeneration (ARMD) and to provide recommendations on the use of these modalities in natural history studies and interventional clinical trials.  A panel of retina specialists participated in a systematic debate on the relevance of distinct imaging modalities held in 2 consensus meetings.  During the CAM, a consortium of international experts evaluated the advantages and disadvantages of various imaging modalities on the basis of the collective analysis of a large series of clinical cases.  A systematic discussion on the role of each modality in future studies in non-neovascular and neovascular ARMD was held.  Main outcome measures were advantages and disadvantages of current retinal imaging technologies and recommendations for their use in advanced ARMD trials.  Imaging protocols to detect, quantify, and monitor progression of atrophy should include color fundus photography (CFP), confocal fundus auto-fluorescence (FAF), confocal near-infrared reflectance (NIR), and high-resolution OCT volume scans.  These images should be acquired at regular intervals throughout the study.  In studies of non-neovascular ARMD (without evident signs of active or regressed neovascularization [NV] at baseline), CFP may be sufficient at baseline and end-of-study visit.  Fluorescein angiography (FA) may become necessary to evaluate for NV at any visit during the study.  Indo-cyanine green angiography (ICG-A) may be considered at baseline under certain conditions.  For studies in patients with neovascular ARMD, increased need for visualization of the vasculature must be taken into account.  Accordingly, these studies should include FA (recommended at baseline and selected follow-up visits) and ICG-A under certain conditions.  The authors concluded that a multi-modal imaging approach is recommended in clinical studies for the optimal detection and measurement of atrophy and its associated features.  Specific validation studies will be necessary to determine the best combination of imaging modalities, and these recommendations will need to be updated as new imaging technologies become available in the future.

Fleckenstein and associates (2018) noted that geographic atrophy (GA) is an advanced form of ARMD that leads to progressive and irreversible loss of visual function.  Geographic atrophy is defined by the presence of sharply demarcated atrophic lesions of the outer retina, resulting from loss of photoreceptors, retinal pigment epithelium (RPE), and underlying choriocapillaris.  These lesions typically appear first in the peri-foveal macula, initially sparing the foveal center, and over time often expand and coalesce to include the fovea.  Although the kinetics of GA progression are highly variable among individual patients, a growing body of evidence suggested that specific characteristics may be important in predicting disease progression and outcomes.  This review synthesized current understanding of GA progression in ARMD and the factors known or postulated to be relevant to GA lesion enlargement, including both affected and fellow eye characteristics.  In addition, the roles of genetic, environmental, and demographic factors in GA lesion enlargement were discussed.  Overall, GA progression rates reported in the literature for total study populations ranged from 0.53 to 2.6 mm2/year (median of approximately 1.78 mm2/year), assessed primarily by color fundus photography or FAF imaging.  Several factors that could inform an individual's disease prognosis have been replicated in multiple cohorts: baseline lesion size, lesion location, multi-focality, FAF patterns, and fellow eye status.  Because BCVA does not correspond directly to GA lesion enlargement due to possible foveal sparing, alternative assessments are being explored to capture the relationship between anatomic progression and visual function decline, including micro-perimetry, low-luminance VA, reading speed assessments, and patient-reported outcomes.  The authors concluded that understanding GA progression and its individual variability is critical in the design of clinical studies, in the interpretation and application of clinical trial results, and for counseling patients on how disease progression may affect their individual prognosis.

Automated Color Fundus Photography for Screening and Detection of Age-Related Macular Degeneration

Peng and associates (2019) noted that in assessing the severity of age-related macular degeneration (ARMD), the Age-Related Eye Disease Study (AREDS) Simplified Severity Scale predicts the risk of progression to late ARMD.  However, its manual use requires the time-consuming participation of expert practitioners.  Although several automated deep learning systems have been developed for classifying CFP of individual eyes by AREDS severity score, none to-date has used a patient-based scoring system that uses images from both eyes to assign a severity score.  DeepSeeNet, a deep learning model, was developed to classify patients automatically by the AREDS Simplified Severity Scale (score 0 to 5) using bilateral CFP.  DeepSeeNet was trained on 58,402 and tested on 900 images from the longitudinal follow-up of 4,549 subjects from AREDS.  Gold standard labels were obtained using reading center grades.  DeepSeeNet simulated the human grading process by first detecting individual ARMD risk factors (drusen size, pigmentary abnormalities) for each eye and then calculating a patient-based ARMD severity score using the AREDS Simplified Severity Scale.  Main outcome measures were overall accuracy, specificity, sensitivity, Cohen's kappa, and area under the curve (AUC).  The performance of DeepSeeNet was compared with that of retinal specialists.  DeepSeeNet performed better on patient-based classification (accuracy = 0.671; kappa = 0.558) than retinal specialists (accuracy = 0.599; kappa = 0.467) with high AUC in the detection of large drusen (0.94), pigmentary abnormalities (0.93), and late AMD (0.97).  DeepSeeNet also out-performed retinal specialists in the detection of large drusen (accuracy 0.742 versus 0.696; kappa 0.601 versus 0.517) and pigmentary abnormalities (accuracy 0.890 versus 0.813; kappa 0.723 versus 0.535); but showed lower performance in the detection of late ARMD (accuracy 0.967 versus 0.973; kappa 0.663 versus 0.754).  The authors concluded that by simulating the human grading process, DeepSeeNet demonstrated high accuracy with increased transparency in the automated assignment of individual patients to ARMD risk categories based on the AREDS Simplified Severity Scale.  These researchers stated if these results are tested and validated by further reports of superiority across multiple datasets (ideally from different countries), it is possible that the integration of deep learning models into clinical practice might become increasingly acceptable to patients and ophthalmologists.  These investigators stated that in the future, deep learning models might support eye services by reducing the time and human expertise needed to classify retinal images and might lend themselves well (through telemedicine approaches) to improving care in geographical areas where current services are absent or limited.  Although deep learning models are often considered “black-box” entities (because of difficulties in understanding how algorithms make their predictions), these researchers aimed to improve the transparency of DeepSeeNet by constructing it from sub-networks with clear purposes (e.g., drusen detection) and analyzing its out-puts with saliency maps.  These efforts to demystify deep learning models may help improve levels of acceptability to patients and adoption by ophthalmologists.  These investigators have also analyzed the performance of several distinct training strategies; lessons from these approaches may have applicability to the development of deep learning models for other retinal diseases, such as diabetic retinopathy, and even for image-based deep learning systems outside of ophthalmology.

The authors stated that this study had several drawbacks.  One current limitation of DeepSeeNet (at least in its present iteration) arose from the imbalance of cases that were available in the AREDS data-set used for its training, especially the relatively low proportion of participants with late ARMD, which likely contributed to the relatively lower accuracy of DeepSeeNet in the classification of late ARMD, that is, through the performance of LA-Net in the overall model.  However, this limitation may potentially be addressed by further training using image data-sets with a higher proportion of late ARMD cases.  A limitation of this data-set included the sole use of CFP because these were the only images obtained in a study that began in 1992.  Other imaging techniques such as OCT and FAF images were not yet feasible or universally available.  Future studies would benefit from inclusion of additional methods of imaging, and multi-modal imaging would be desirable.  Another potential drawback lied in the reliance of DeepSeeNet on higher levels of image quality for accurate classification.  Unlike in other studies, these investigators did not perform extensive pre-processing of images, such as the detection of the outer boundaries of the retina or normalization of the color balance and local illumination.  It was possible that the use of these techniques might have improved the accuracy of the model.  However, these researchers deliberately avoided extensive pre-processing to make their model as generalizable as possible.  They recommended further testing of their deep learning model using other data-sets of color fundus images.  Furthermore, it would be interesting for future studies to compare the accuracy of the model with that of different groups of ophthalmologists (e.g., retinal specialists, general ophthalmologists, and trainee ophthalmologists).  Indeed, a recent study on grader variability for diabetic retinopathy severity using CFP suggested that retinal specialists had a higher accuracy than that of general ophthalmologists.  In this study, these researchers set the bar as high as possible for the deep learning model, because they considered that the retinal specialists might have accuracy as close as possible to that of the Reading Center gradings.

Pead and colleagues (2019) stated that the rising prevalence of age-related eye diseases, especially ARMD, places an ever-increasing burden on healthcare providers.  As new treatments emerge, it is necessary to develop methods for reliably assessing patients' disease status and stratifying risk of progression.  The presence of drusen in the retina represents a key early feature where size, number and morphology are thought to correlate significantly with risk of progression to sight-threatening ARMD.  Manual labeling of drusen on CFP by a human is labor-intensive and is where automatic computerized detection would appreciably aid patient care.  These investigators evaluated current artificial intelligence methods and developments for the automated detection of drusen in the context of ARMD.  The authors concluded that for automated drusen assessment to be employed in the clinic it must go beyond cross-sectional phenotyping and instead relate to real patient visual outcomes; and longitudinal studies are needed to determine if automated image grading, based on drusen detection, could accurately predict disease progression.  These researchers stated that future algorithms involving drusen detection should aim to provide useful quantification to aid screening for ARMD.  A screening program should stratify patients according to optimal follow-up pathway.  In order for automated drusen detection to contribute to the cost-effectiveness of a screening program for ARMD, it must separate individuals with drusen associated with normal aging from patients whose drusen load progresses as well as stratifying patients with mild ARMD into those at low-risk and at high-risk of progression to severe ARMD.  This would enable the ophthalmologist to select relevant patients for regular follow-up, thus improving the efficiency of patient care.

Evaluation of Eye Injury

In an observational, case-series study, Lavinsky and colleagues (2011) reported FAF and OCT findings in patients with blunt ocular trauma.  A total of 6 eyes of 6 consecutive patients with blunt ocular trauma were evaluated using color fundus photography, the Heidelberg Retina Angiograph 2 (HRA2) system for FAF and OCT (Stratus OCT); 3 patients presented with secondary retinal pigment epitheliopathy that was identified as a reduced FAF plaque with interposed increased FAF granular smaller lesions.  These findings were not as evident in fundus examination and color photography in 2 patients.  Visual field in 1 patient showed a decreased area of sensitivity that correlated to the reduced/increased auto-fluorescent lesion.  The other 3 patients had sub-retinal hemorrhage and choroidal rupture, which appeared with a reduced FAF with an increased FAF rim after resolution; OCT demonstrated a chorio-capillaris/RPE complex disruption and its resolution over time in all patients with choroidal rupture.  The authors concluded that damaged RPE area was more evident and better delineated by FAF imaging compared with fundus examination and fundus photography alone.  They stated that auto-fluorescence imaging might be a useful examination to show the length and severity of post-traumatic retinal lesions and it may add relevant information in the global evaluation of blunt ocular trauma complications.  Moreover, OCT added valuable information to the diagnosis and progression of choroidal rupture.  These researchers stated that further studies are needed to determine the predictive value of FAF in ocular blunt trauma.

An UpToDate review on “Approach to eye injuries in the emergency department” (Gardiner, 2019a) does not mention fundus photography and posterior segment scanning as management tools.

Furthermore, an UpToDate review on “Overview of eye injuries in the emergency department” (Gardiner, 2019b) states that “In patients with vitreous hemorrhage that obscures the fundus but who have a closed globe, orbital ultrasound can identify a retinal detachment”.  This review does not mention “posterior segment scanning”.

Neurofibromatosis Type 1

Makino and Tampo (2013) reported a case of rare and unusual choroidal abnormalities in a 42-year old woman with systemic lupus erythematosus (SLE).  Images were obtained using fundus photography, fluorescein angiography (FA), NIR imaging, and OCT.  The patient had a history of SLE and central retinal artery occlusion in her right eye.  Fundus examination showed no specific retino-choroidal abnormalities, with the exception of optic disc atrophy in her right eye and a peripapillary small hemorrhage in her left eye.  However, NIR revealed multiple bright patchy lesions in the choroid of the posterior pole and the mid-periphery of the fundus in both eyes; OCT demonstrated irregular hyper-reflectivity at the lesion sites.  The authors concluded that observed choroidal abnormalities were highly specific findings and thus, were indicative of neurofibromatosis type 1 (NF1).  Since the co-existence of SLE and NF1 is extremely rare, this case provided the chance to examine the relationship between SLE and NF1.

Abdolrahimzadeh et al (2014) stated that NF1 is an autosomal dominant disorder involving aberrant proliferation of multiple tissues of neural crest origin.  Retinal vascular alterations in NF1 have rarely been reported in the literature and their nature is unclear.  In a retrospective study, these researchers described distinctive retinal microvascular alterations and their relationship to choroidal nodules in patients with NF1.  Records of 17 consecutive patients with diagnosis of NF1, presenting Lisch nodules and choroidal alterations, and 17 age- and gender-matched healthy control patients were evaluated.  Fundus photographs, NIR and enhanced depth imaging -- OCT images were reviewed.  Retinal microvascular abnormalities and choroidal and retinal alterations in proximity of the retinal microvascular alterations were carefully noted.  A total of 6 patients (35 %) presented distinctive microvascular abnormalities.  These consisted of small, tortuous vessels with a "spiral" or "corkscrew" aspect.  They were 2nd or 3rd order, small tributaries of the superior or inferior temporal vein.  These vessels were all located overlying choroidal alterations as observed with NIR.  Enhanced depth imaging -- OCT showed alteration of choroidal vasculature due to the presence of choroidal nodules but otherwise retinal and choroidal cross-sections were unremarkable for morphology.  The authors concluded that retinal microvascular alterations overlying choroidal nodules in patients with NF1 could be considered another distinctive characteristic of the disease.  Although the nature of these alterations was unclear, the authors speculated that functional disorders of vasomotor nerve cells, which originated in the embryonal neural crest could lead to their formation.

Furthermore, an UpToDate review on “Neurofibromatosis type 1 (NF1): Management and prognosis” (Korf et al, 2020) does not mention fundus photography as a management tool.

Pigment Dispersion Syndrome

According to the American Academy of Ophthalmology (AAO, 2019), pigment dispersion syndrome (PDS) occurs when the pigment rubs off the back of one’s iris.  This pigment then floats around to other parts of the eye.  The tiny bits of pigment can clog the eye's drainage angle, which can cause eye pressure problems.  Because there are often no symptoms, PDS is usually diagnosed during a regular eye examination.  During a thorough eye examination, the ophthalmologist will:

• Check the intra-ocular pressure (IOP)
• Do other tests like a gonioscopy, if PDS is suspected.  This lets the ophthalmologist look at the eye's drainage angle.  He or she can see if something is blocking the fluid from leaving the eye.
• These tests are the same used for a glaucoma diagnosis and will determine if one has pigmentary glaucoma.  The ophthalmologist will be looking for tell-tale signs of pigment floating in the eye (including at the back of the cornea) or small sections of pigment missing from one’s iris.

The AAO does not mention fundus photography as a management tool. Pigment Dispersion Syndrome Diagnosis

Tamoxifen Users

The Prescribing Information of tamoxifen (Soltamox) notes that “Ocular disturbances, including corneal changes, decrement in color vision perception, retinal vein thrombosis, and retinopathy have been reported in patients receiving tamoxifen.  An increased incidence of cataracts and the need for cataract surgery have also been reported.  Patients should be advised to seek medical attention if they experience any visual disturbance”.  However, it does not mention monitoring of vision in patients taking the drug.  Prescribing Information.

Appendix

Note on Optomap coding: The Optos Optomap is image-assisted ophthalmoscopy for evaluation of ocular health.  Optomap meets the criteria for the CPT code for fundus photography (92250).

Table: CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Information in the [brackets] below has been added for clarification purposes.   Codes requiring a 7th character are represented by "+":
Fundus photography:
CPT codes covered if selection criteria are met:
92250	Fundus photography with interpretation and report [includes Optomap]
CPT codes not covered if selection criteria are met:
0380T	Computer-aided animation and analysis of time series retinal images for the monitoring of disease progression, unilateral or bilateral, with interpretation and report
Other HCPCS code related to the CPB:
Ethambutol - no specific code :
ICD-10 codes covered if selection criteria are met:
A52.15	Late syphilitic neuropathy
B20	Human immunodeficiency virus (HIV) disease
B39.4	Histoplasmosis capsulati, unspecified
B39.5	Histoplasmosis duboisii
B39.9	Histoplasmosis, unspecified
B50.0 - B54	Malaria
B58.01	Toxoplasma chorioretinitis
B58.09	Other toxoplasma oculopathy
C69.00 - C69.92	Malignant neoplasm of eye and adnexa
C79.40 - C79.49	Secondary malignant neoplasm of other and unspecified parts of nervous system
D09.20 - D09.22	Carcinoma in situ of eye
D31.20 - D31.22	Benign neoplasm of retina
D31.30 - D31.32	Benign neoplasm of choroid
D31.40 - D31.42	Benign neoplasm of ciliary body
D33.3	Benign neoplasm of cranial nerves
D49.81	Neoplasm of unspecified behavior of retina and choroid
D57.00 - D57.819	Sickle-cell disorders
E08.00 - E13.9	Diabetes mellitus
E70.20 - E70.9	Disorders of aromatic amino-acid metabolism
G35	Multiple sclerosis
G93.2	Benign intracranial hypertension [pseudotumor cerebri]
H27.10 - H27.119	Subluxation of lens
H27.131 - H27.139	Posterior dislocation of lens
H30.001 - H30.93	Chorioretinal inflammation
H31.00 - H31.9	Other diseases of choroid
H32	Chorioretinal disorders in diseases classified elsewhere
H33.001 - H33.8	Retinal detachment and breaks
H34.00 - H34.9	Retinal vascular occlusions
H35.00 - H35.9	Other retinal disorders
H36	Retinal disorders in diseases classified elsewhere
H40.001 - H40.9	Glaucoma
H42	Glaucoma in diseases classified elsewhere
H43.00 - H43.9	Disorders of vitreous body
H44.001 - H44.9	Disorders of the globe
H44.511 - H44.519	Absolute glaucoma
H46.00 - H47.9	Disorders of optic nerve and visual pathways
H53.50 - H53.59	Color vision deficiencies
H59.031 - H59.039	Cystoid macular edema following cataract surgery
L93.0 - L93.2	Lupus erythematosus
M05.00 - M14.89	Inflammatory polyarthropathies
M32.0 - M32.9	Systemic lupus erythematosus (SLE)
P35.0	Congenital rubella syndrome
Q13.4	Other congenital corneal malformations [Peter’s anomaly]
Q14.0 - Q14.9	Congenital anomalies of posterior segment of eye
Q15.0	Congenital glaucoma
Q85.1	Tuberous sclerosis
Q85.8 - Q85.9	Other and unspecified phakomatoses, not elsewhere classified
Q87.1 - Q87.89	Other specified congenital malformation syndromes affecting multiple systems
Q89.8	Other specified congenital malformations
Q99.2	Fragile X chromosome
R94.110	Abnormal electro-oculogram (EOG)
R94.111	Abnormal electroretinogram [ERG]
R94.112	Abnormal visually evoked potential [VEP]
R94.113	Abnormal oculomotor study
S05.50x+ - S05.52x+	Penetrating wound with foreign body of eyeball
T37.2x1+ - T37.2x4+	Poisoning by antimalarials and drugs acting on other blood protozoa [hydroxychloroquine toxicity]
T37.3x1+ - T37.3x4+	Poisoning by other antiprotozoal drugs
ICD-10 codes not covered for indications listed in the CPB (not all inclusive):
B83.0	Visceral larva migrans
H21.231 - H21.239	Degeneration of iris (pigmentary) [pigment dispersion syndrome]
Q85.01	Neurofibromatosis, type 1
S05.00xx - S05.02xx	Injury of conjunctiva and corneal abrasion without foreign body
S05.10xx - S05.12xx	Contusion of eyeball and orbital tissues
Z01.1	Encounter for examination of eyes and vision
Z13.5	Encounter for screening for eye and ear disorders
Z79.810	Long term (current) use of selective estrogen receptor modulators (SERMs) [tamoxifen]
Automated color fundus photography:
CPT codes not covered if selection criteria are met:
Automated color fundus photography- no specific code:
ICD-10 codes not covered for indications listed in the CPB:
H35.311x - H35.319x	Nonexudative age-related macular degeneration
H35.321x -H35.329x	Exudative age-related macular degeneration

The above policy is based on the following references: