Aetna considers critical flicker fusion in the diagnosis of visual acuity experimental and investigational as the clinical evidence is not sufficient to permit conclusions on the health outcome effects of critical flicker fusion in the diagnosis of visual acuity.

Aetna considers critical flicker fusion experimental and investigational for the diagnosis of low-grade (minimal) hepatic encephalopathy because its effectiveness for this indication has not been established.

Critical flicker fusion (CFF) is the rate of flicker at which one perceives no flicker.  The clinical evidence is insufficient to permit conclusions on the health outcome effects of critical flicker fusion in the diagnosis of visual acuity. 

In continuing to develop a potential vision test based on the CFF phenomenon by using a brighter stimulus and optimizing its size, Shankar and Pesudovs (2007) reported the results of a prospective non-randomized study in which 225 participants were assigned to 1 of 4 groups: normal, media opacity only, retinal/neural disease only, and cataract plus retinal/neural disease.  The CFF thresholds were measured for 3 stimulus sizes: 0.5 degree, 1.0 degree, and 1.5 degrees.  Discrimination between groups was tested by analysis of variance and receiver operating characteristic analysis.  The relationship between visual acuity and CFF in eyes without media opacity was determined by linear regression and used to predict visual outcomes in 23 eyes having cataract surgery.  The mean age of the 225 participants was 71.4 years +/- 13.2 (SD); 134 (59.8 %) were women.  The normal group had 41 participants, and the other 3 groups had 61 participants each.  Critical flicker fusion thresholds were reduced in retinal/neural disease but resistant to image degradation from media opacity.  The 1.5-degree stimulus had 88 % sensitivity and 90 % specificity for discriminating groups.  Visual acuity after cataract surgery was accurately predicted within +/-1 line in 43 % of eyes, +/-2 lines in 83 %, and +/-3 lines in 100 %.  All eyes with poor visual acuity (greater than 0.50 logMAR) or dense cataract (greater than 4.0 Lens Opacities Classification System III) were predicted within +/-2 lines.  The authors concludedthat the CFF phenomenon effectively discriminated between subjects with and without retinal/neural disease and accurately predicted visual outcome after cataract surgery.  The use of a brighter stimulus enhanced performance in cases of dense media opacity. 

Vianya-Estop et al (2004) determined whether CFF thresholds fulfill the criteria for a potential vision test (PVT) by being unaffected by media opacity yet affected by retinal disease.  Critical flicker fusion thresholds for 3 different stimulus sizes (0.5, 1.0, and 1.5 degrees) were measured in 72 patients (mean age of 78.43 +/- 7.07 years) comprising 31 subjects with media opacity, 21 with macular disease, and 20 with pseudophakia.  There were no statistically significant differences between CFF values from the media opacity and the pseudophakia groups for any target size (p > 0.10).  However, CFF values were significantly lower in patients with macular disease for all the target sizes (p < 0.05).  Analysis of a subset of 6 subjects with media opacity and 7 subjects with macular disease and visual acuity of 20/200 or worse showed the media opacity group still had similar CFF values as the pseudophakia group and had significantly higher CFF than the macular disease group.

Del Romo and colleagues (2006) reported the details of the clinical utility of CFF as a PVT (which attempts to predict the visual outcome that might be expected as a result of a cataract operation).  ritical flicker fusion thresholds were determined in 31 subjects with age-related idiopathic cataract and no other eye disease, 19 subjects with macular disease (MD) and clear ocular media, and 24 age-matched control subjects.  In addition, the CFF technique was administered before cataract surgery in 52 patients and compared with the information provided by pre-surgical case history and ocular examination alone (ophthalmological judgment [OJ]) and results from 2 commonly used PVTs (the retroilluminated pinhole and the potential acuity meter).  ritical flicker fusion thresholds obtained in the nonsurgical cataract group were unrelated to cataract severity and were similar to those in the control group.  In contrast, CFF scores were significantly related to visual acuity (VA) in the MD group.  In the pre- and post-surgical studies, OJ predicted postoperative VA very well in patients with moderate cataract and normal fundi and better than all the PVTs.  Ophthalmological judgment performed less well in patients with comorbid eye disease and dense cataracts, when information from the PVTs would probably have been useful.  Critical flicker fusion provided the most accurate predictions of postoperative VA in the small sample of patients with dense cataracts.  The authors concluded, “CFF was unaffected by cataract, yet sensitive to MD, and provided useful information about the postoperative visual outcome beyond that obtained through history and ocular examination in patients with dense cataracts”.

Vianya-Estopa et al (2006) evaluated the usefulness of a battery of PVTs including potential acuity meter (PAM), laser interferometer (LI), CFF, superilluminated pinhole at distance (SPH(d)) and near (SPH(n)), and optimal reading speed (ORS) by their independence of the effects of cataracts and sensitivity to MD in 76 patients with age-related cataract and no other eye disease, 52 patients with MD and clear ocular media, and 28 patients with normal, healthy eyes.  Potential vision tests were independent of the degrading effects of cataract up to a visual acuity (VA) level of 20/200 or worse (CFF), 20/125 (ORS and SPH), and 20/40 (PAM and LI).  A high degree of association was found between PVT scores and distance VA in the MD group for SPH(d) (r2 = 0.93), SPH(n) (r2 = 0.89), and PAM (r2 = 0.71).  A moderate correlation was found for LI (r2 = 0.55), CFF (r2 = 0.50), and ORS (r2 = 0.45).  The authors concluded, “in regard to critical flicker/fusion frequency that while the test showed the greatest ability to bypass cataracts, its ability to predict VA in patients with early MD was limited”.

Trick (2003) noted that the temporal processing capability of the visual system has historically been evaluated by measuring sensitivity to flicker.  The sensation of flicker occurs when light stimulation is intermittent rather than continuous.  In general, as the flicker frequency increases, a point is reached at which the perception of flicker is lost and the light appears continuous or fused.  This point is known as the CFF frequency.  Trick wrote that CFF is one of many techniques and tools available to measure aspects of visual function that extend beyond visual acuity.

Goldbecker et al (2013) stated that hepatic encephalopathy (HE) is a common complication of liver insufficiency.  While there is widespread acceptance of its importance, there is no consensus on how best to diagnose and monitor HE.  These investigators compared the 4 most favored methods for the diagnosis of HE.  A total of 170 patients who were on the waiting list for liver transplantation as well as 86 healthy controls were included in the study.  All patients and controls underwent the porto-systemic encephalopathy syndrome test yielding the psychometric hepatic encephalopathy score (PHES), the repeatable battery for the assessment of neuropsychological status (RBANS), the inhibitory control test (ICT) and CFF measurement.  Psychometric hepatic encephalopathy score and ICT targets had the best sensitivity (85.7 % versus 85.7%) and specificity (96.5 % versus 97.6 %) for the diagnosis of overt HE.  Critical flicker fusion showed inferior sensitivity (40.9 %) for the diagnosis of HE and dependency from previous alcohol abuse (p = 0.015).  Multiple regression analysis showed that all test results apart from PHES were influenced by secondary diagnoses such as diabetes mellitus and renal insufficiency.  The authors concluded that in the German population of patients awaiting liver transplantation, PHES is the most robust method for the diagnosis and follow-up of HE.

Kircheis et al (2014) stated that CFF and PHES analyses are widely used to diagnose HE, but little is known about their value in the diagnosis of low-grade HE.  The diagnostic values of CFF and PHES were compared using a computerized test battery and West Haven criteria as reference.  These investigators performed CFF analysis on 559 patients with cirrhosis and 261 without (controls).  Of these 820 patients, 448 were evaluated using a modified PHES system and 148 were also evaluated using the conventional PHES system.  Critical flicker fusion distinguished between patients with overt HE and without minimal or overt HE in the entire study population with 98 % sensitivity and 94 % specificity and in the subgroup of patients who were evaluated by conventional PHES with 97 % sensitivity and 100 % specificity.  Conventional PHES identified patients with overt HE with 73 % sensitivity and 89 % specificity.  Critical flicker fusion distinguished between patients with and without minimal HE with only 37 % sensitivity but 94 % specificity (entire study population).  In the subgroup of patients evaluated by conventional PHES, CFF distinguished between patients with and without minimal HE with 22 % sensitivity and 100 % specificity; these values were similar to those for conventional PHES (30 % sensitivity and 89 % specificity).  The modified PHES distinguished between patients with and without minimal HE with 49 % sensitivity and 74 % specificity.  The diagnostic agreement values between CFF and conventional or modified PHES in patients with minimal HE were only 54 % or 47 %, respectively.  The authors concluded that in an analysis of patients with cirrhosis and controls, CFF distinguished between patients with overt HE and without minimal or overt HE.  Psychometric hepatic encephalopathy score testing produced a statistically significant difference among groups, but there was considerable overlap between controls and patients with overt HE.  Moreover, these researchers stated that PHES, CFF, and a combination of PHES and CFF could not reliably distinguish patients with minimal HE from controls or those with overt HE.

An UpToDate review on “Hepatic encephalopathy in adults: Clinical manifestations and diagnosis” (Ferenci, 2014) states that “Electrophysiologic tests to detect minimal hepatic encephalopathy include EEG monitoring, evoked potentials, and critical flicker frequency testing.  However, none of these tests is widely used …. Retinal glial cells are involved in ammonia detoxification by glutamine synthesis.  In patients with liver failure, they exhibit morphological changes similar to those observed in brain astrocytes, suggesting that retinal gliopathy could serve as a marker of cerebral gliopathy in patients with hepatic encephalopathy.  These observations provided the rationale for the development of a visual test (the critical flicker/fusion frequency) for determining whether hepatic encephalopathy is present.  Advantages of the test are that it is objective and it is not affected by the patient's age or education/literacy level.  However, a meta-analysis suggests that it is only moderately sensitive for detecting minimal hepatic encephalopathy.  The meta-analysis included 9 studies with 622 patients and found that critical flicker frequency had a sensitivity for detecting minimal hepatic encephalopathy of 61 % and a specificity of 79 %”.