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Policy

Policy Guidelines

Benefit Application

Rationale

The use of various techniques of retinal nerve fiber analysis (including scanning laser ophthalmoscopy, scanning laser polarimetry, and optical coherence tomography) for the diagnosis and management of glaucoma were addressed by a 2001 (1) and 2003 TEC Assessment. (2) The 2003 Assessment offered the following observations (2):

The 2003 TEC Assessment (2) offered the following conclusions:

• No randomized trials compare the health outcomes of management guided by conventional tests alone to outcomes of management guided by conventional tests plus RNFLA in the detection or monitoring of POAG.
• The best available evidence on using RNFLA to predict visual loss comes from a study of scanning laser ophthalmoscopy (i.e., Heidelberg retinal tomography, HRT), in which 21 patients progressed from ocular hypertension to glaucoma (converters) and 164 patients did not progress (nonconverters). Of the 21 converters, 13 had abnormal HRT results; in 11 of these, the tests were positive before development of visual field defects (average lead time was 5.4 months). Of the 164 nonconverters, 47 had abnormal results. (3)
• The positive predictive value of HRT, given the available data, was 22%. The frequency of true positives and false positives in the Kamal et al study may depend on the duration of follow-up completed in this study, which was a mean of at least 33 months. If the frequency of true and false positives stays the same with more adequate follow-up, the consequence would be overtreatment in 78% of patients with a positive HRT. Additional follow-up is needed to show whether some false positives are late converters who become true positives.
• Cross-sectional studies do not inform about the prediction of future visual loss. These studies can reveal whether RNFLA can detect prevalent cases of glaucoma. RNFLA does not detect all prevalent cases; it is falsely negative in 14%–36% of cases among recent cross-sectional studies using predetermined diagnostic criteria or blinded test interpretation.
• The available evidence does not permit conclusions about whether RNFLA predicts visual loss or whether its use would improve health outcomes by preserving vision.

Regarding optic nerve head analyzers, pulsatile ocular blood flow, or blood flow velocity (techniques not addressed by the TEC Assessment), there are similar deficiencies reported in the published literature. Specifically, no data from published clinical trials document how these devices should be incorporated into clinical practice and whether treatment decisions based on the use of these devices result in improved patient outcomes compared with the conventional methods of evaluation. Additional information is also needed to 1) document the association between blood flow and glaucoma; 2) determine the relevant vessels for study considering the complex blood supply to the optic nerve; and 3) establish the range of normal values, particularly in relation to other factors such as blood pressure, heart rate, and compliance of the blood vessels. (4-8)

Evidence Subsequent to the 2003 TEC Assessment

Annual literature searches (2004, 2005, and 2006) were performed to identify relevant recent evidence focusing on longitudinal results as emphasized in the TEC Assessment. Results are summarized below.

The Confocal Scanning Laser Ophthalmoscopy (CSLO) Ancillary Study, a subset of the Ocular Hypertension Treatment Study (OHTS), was designed to determine whether annual optic disk topographic measurements can accurately predict visual field loss. (9) The OHTS randomized patients with elevated intraocular pressure to either topical hypotensive medication or observation. Baseline data reported from the CSLO Ancillary Study did not allow reaching conclusions about how well RNFL analysis measurements predict visual loss over time.

Follow-up of the CSLO Ancillary Study was reported in 2005. (10) Of 438 participants 34% had abnormal CSLO values according to HRT criteria. The average interval between CSLO exams to POAG was 48.4 months (SD 25.2). Eyes not developing POAG were followed up a mean of 79.5 months (SD 20.8). Sensitivity of CSLO for development of POAG using HRT criteria was 55.6% (95% CI: 39.6 to 70.5), specificity 68.2% (95% CI: 63.5 to 72.5), and positive predictive value 13.5% (95% CI: 8.9 to 20.0). The investigators concluded that '[t]he current analysis did not directly determine whether the prediction model that includes baseline CSLO measurements is improved over the OHTS prediction model that includes baseline stereophotographic cup-disc ratio measurements…. Longer follow-up is required to evaluate the true predictive accuracy of CSLO measures.'

Longitudinal results have also been reported from the UCSD Diagnostic Innovations in Glaucoma Study (DIGS). (11,12) In the first publication, eyes from 160 glaucoma suspects evaluated with scanning laser polarimetry (SLP) were followed for 1.7 to 4.1 years. Visual field damage developed in 16 (10%) participants. Only relative risks for visual field damage were reported as opposed to sensitivities, specificities, and predictive values. (11) From 12 SLP parameters and a 13 th calculated from those parameters, 3 were significantly associated with the visual field outcome in multivariate analyses (models were incorrectly specified owing to the small number of outcomes). In a subsequent report, 114 glaucoma suspects were examined with OCT (one eye per patient). (12) Over a 4.2-year average follow-up, 23 (20%) developed changes consistent with glaucoma. While the relative risk of developing glaucomatous changes was increased with thinner RNFL results (1.5-fold with per 10μm), sensitivities and specificities were not reported demonstrating clinical utility.

At Manchester Royal Eye Hospital (UK), HRT and GDx systems were evaluated in cross-sectional (98 normal controls and 152 patients with POAG) and longitudinal studies (240 at risk of developing glaucoma due to high intraocular pressure or fellow eye with POAG and 75 with POAG). (12) With specificity set at 95%, sensitivities of the HRT and GDx in detecting POAG were 59% and 45%, respectively, in the cross-sectional study. In the longitudinal study, patients were evaluated biannually over an average 3.5 year follow-up. Evidence of visual field defects developed in 72 of the at risk group. Poor agreement was found between the HRT and GDx for development of visual field abnormalities. Although sensitivities might vary according to definitions for conversion to a visual field defect, among patients with baseline HRT and GDx abnormalities, sensitivities could be as low as 13% to 39%. The authors concluded that “on account of the fact that the HRT and GDx fail to detect a significant number of cases of conversion, they cannot provide a replacement for visual field examination.”

Kalaboukhova et al.enrolled 55 patients with OHT and POAG (34 and 25 respectively) a median of 47 months (range 22-86). (13) HRT was performed at entry (1998-2002) and re-examined between 2001 and 2005. Based on optic disk photographs, eyes were classified as progressive or stable—22 showed progression. From 25 parameters evaluated, 5 were accompanied by statistically significant areas under the ROC curve. However, there were no adjustments for multiple comparisons; the sample was small and one of convenience.

Accordingly, studies published since the 2003 TEC Assessment support its conclusions.

Finally, the American Academy of Ophthalmology POAG Suspect and POAG Preferred Practice Patterns recommend evaluating the optic nerve and retinal nerve fiber layer. (14,15) The documents also state that “[t]he preferred technique for optic nerve head and retinal nerve fiber layer evaluation involves magnified stereoscopic visualization (as with the slit-lamp biomicroscope), preferably through a dilated pupil.”

References:

1. 2001 TEC Assessment; Volume 16, Number 13
2. 2003 TEC Assessment; Volume 18, Number 7
3. Kamal DS, Garway-Heath DF, Hitchings RA et al. Use of sequential Heidelberg retina tomograph images to identify changes at the optic disc in ocular hypertensive patients at risk of developing glaucoma. Br J Ophthalmol 2000; 84(9):993-8.
4. Cioffi GA. Three assumptions: ocular blood flow and glaucoma. J Glaucoma 1998; 7(5):299-300.
5. Fontana L, Poinoosawmy D, Bunce CV et al. Pulsatile ocular blood flow investigation in asymmetric normal tension glaucoma and normal subjects. Br J Ophthalmol 1998; 82(7):731-6.
6. James CB. Pulsatile ocular blood flow. Br J Ophthalmol 1998; 82(7):720-1.
7. Kaiser HJ, Schoetzau A, Stumpfig D et al. Blood-flow velocities of the extraocular vessels in patients with high-tension and normal-tension primary open-angle glaucoma. Am J Ophthalmol 1997; 123(3):320-7.
8. Rankin SJ, Walman BE, Buckley AR et al. Color Doppler imaging and spectral analysis of the optic nerve vasculature in glaucoma. Am J Ophthalmol 1995; 119(6):685-93.
9. Zangwill LM, Weinreb RN, Berry CC et al. The confocal scanning laser ophthalmoscopy ancillary study to the ocular hypertension treatment study: study design and baseline factors. Am J Ophthalmol 2004; 137(2):219-27.
10. Zangwill LM, Weinreb RN, Beiser JA et al. Baseline topographic optic disc measurements are associated with the development of primary open-angle glaucoma: the Confocal Scanning Laser Ophthalmoscopy Ancillary Study to the Ocular Hypertension Treatment Study. Arch Ophthalmol 2005; 123(9):1188-97.
11. Mohammadi K, Bowd C, Weinreb RN et al. Retinal nerve fiber layer thickness measurements with scanning laser polarimetry predict glaucomatous visual field loss. Am J Ophthalmol 2004; 138(4):592-601.
12. Lalezary M, Medeiros FA, Weinreb RN et al. Baseline optical coherence tomography predicts the development of glaucomatous change in glaucoma suspects. Am J Ophthalmol 2006; 142(4):576-82.
13. Kalaboukhova L, Fridhammar V, Lindblom B. Glaucoma follow-up by the Heidelberg Retina Tomograph. Graefes Arch Clin Exp Ophthalmol. 2006 Jun; 244(6):654-62.
14. American Academy of Ophthalmology. (2005). Primary open-angle glaucoma suspect. Preferred practice pattern. San Francisco: American Academy of Ophthalmology. Available at: http://www.aao.org/education/library/ppp/upload/Primary_Open_Angle_Glaucoma_Suspect-2.pdf
15. American Academy of Ophthalmology. (2005). Primary open-angle glaucoma. Preferred practice pattern. San Francisco: American Academy of Ophthalmology. Available at: http://www.aao.org/education/library/ppp/upload/Primary_Open_Angle_Glaucoma-2.pdf

Index

Policy History