Purpose
To investigate the correlation between aqueous flare values and central visual function in patients with retinitis pigmentosa (RP).
Design
Retrospective, observational case series.
Methods
We retrospectively studied 160 patients diagnosed with typical RP and 59 control subjects. Aqueous flare values were measured by laser flare cell meter. The relationships between aqueous flare and best-corrected visual acuity (VA) and mean deviation (MD) of static perimetry tests were analyzed in RP patients.
Results
The aqueous flare values were significantly higher in the RP patients compared to the control subjects (10.6 ± 7.9 vs 5.0 ± 2.1 photon counts per millisecond [pc/ms], P < .0001). In the RP patients, the aqueous flare values were negatively correlated with VA ( r = 0.359, P < .0001) and MD ( r = −0.330, P < .0001). Age-subgroup analysis showed a significant correlation between aqueous flare and VA in the RP patients’ 40s, 50s, and 60s and between aqueous flare and MD in the 30s, 40s, 50s, and 60s. The RP patients with MD values ≥−15 decibels (dB) showed significantly higher levels of aqueous flare than those with MD values <−15 dB (12.0 ± 6.2 vs 8.7 ± 5.8, P = .0001).
Conclusions
Aqueous flare is increased in RP patients and negatively correlates with central visual function. These results suggest a close relationship between inflammation and central vision loss in RP.
Retinitis pigmentosa (RP) comprises a group of inherited retinal degeneration disorders that result from photoreceptor cell death. RP affects over 1 million individuals globally. Molecular genetic studies have identified mutations in more than 50 genes that are associated with RP, including the rhodopsin and cyclic guanosine monophosphate phosphodiesterase β-subunit. However, the mechanisms by which these mutations induce rod and cone photoreceptor cell death have not been fully elucidated, and the disease remains intractable.
As suggested by the term “retinitis,” it was initially thought that inflammation is an important part of the pathogenesis of RP. Although the primary cause of RP is now known to be genetic defects in photoreceptor cells or retinal pigment epithelial cells, recent studies have again focused on inflammation as a potential factor that contributes to retinal degeneration. In animal models of RP, it was shown that proinflammatory cytokine/chemokine production and inflammatory cell activation occur in an early phase of retinal degeneration, and that the modulation of inflammatory molecules/cells ameliorates photoreceptor cell death. Vitreous samples of human RP patients showed increased infiltrations of macrophages and lymphocytes. Moreover, we recently demonstrated that the number of inflammatory cells in the anterior vitreous correlates with worse visual function in RP patients, suggesting a possible interaction between inflammation and photoreceptor cell loss in RP. However, that study was limited in that its slit-lamp measurement of intraocular inflammation was subjective and qualitative, and it may not be sensitive enough to evaluate low grades of inflammation.
Laser flare photometry is a noninvasive, objective, and quantitative method to measure aqueous flare with high reproducibility. Aqueous flare values are proportional to the amounts of proteins present, which increase with blood-ocular barrier breakdown and inflammation. Another study found that the aqueous flare values in RP patients were significantly higher than those in control subjects. However, the relationship between aqueous flare and visual function has not been fully evaluated. In the present study, we show that higher aqueous flare values correlate with worse visual function in RP patients, confirming the association between ocular inflammation and central vision by an objective assessment.
Methods
Study Design and Ethics Statement
We retrospectively reviewed the records of patients with RP and control subjects. This study was approved by the Institutional Review Board of the Kyushu University Hospital (Fukuoka, Japan), and was conducted in accord with the tenets of the Declaration of Helsinki on biomedical research involving human subjects. The review board waived the need for written informed consent, because the study design comprised a retrospective chart review.
Patients
Patients were recruited from the Kyushu University Hospital in 2012 and 2013: 160 patients with the diagnosis of typical RP and 59 control subjects without ocular diseases were included. The baseline characteristics of these patients are shown in Table 1 . The diagnosis of typical RP was based on a patient’s history of night blindness, visual field constriction and/or ring scotoma, and markedly reduced or nonrecordable a- and b-wave amplitudes on electroretinography (ERG) testing, in addition to ophthalmoscopic findings (eg, bone spicule–like pigment clumping in the mid-peripheral and peripheral retina and attenuation of retinal vessels). Cystoid macular edema (CME) was detected by optical coherence tomography.
| Control Subjects (n = 59) | Patients With RP (n = 160) | P Value | |
|---|---|---|---|
| Age, y (range) | 54.0 ± 18.5 (22–89) | 48.9 ± 14.1 (17–79) | .1203 |
| Sex (male:female) | 28:31 | 71:89 | .7765 |
| Eyes (n) | 101 | 305 | |
| Flare (pc/ms) | 5.0 ± 2.1 | 10.1 ± 6.0 | <.0001 |
| VA (logMAR) | 0.4 ± 0.6 | ||
| MD value (dB) | −14.4 ± 10.2 a | ||
| Inheritance mode (n) | |||
| AD | 22 | ||
| AR | 23 | ||
| X-linked | 0 | ||
| Spontaneous | 115 |
Excluded from the study were patients who had a history of other ocular diseases or intraocular surgery, or who received antiglaucoma treatment (eg, topical prostaglandin analogues, topical beta blockers, and topical or oral acetazolamide). RP patients who received topical acetazolamide against CME were excluded because acetazolamide was shown to affect aqueous flare values. The best-corrected visual acuity (VA) was measured with a standard Japanese decimal VA chart and was converted to the logarithm of the minimal angle of resolution (logMAR) units.
Visual Field Testing
All patients underwent automated static perimetry testing (Humphrey Field Analyzer [HFA]; Humphrey Instruments, San Leandro, California, USA) using the central 10-2 Swedish Interactive Thresholding Algorithm standard program. The lens was corrected as appropriate for the test distance. Visual field testing was repeated if the test reliability was not satisfactory (fixation loss >20%, false positive >15%, or false negative >33%). The test was examined twice, and the better result was used for the analysis in order to reduce the learning effect. If reliable data were not obtained in repeated tests, the data were not included in the study.
Laser Flare Photometry
The aqueous flare was measured with the Kowa FM-600 laser flare meter (Kowa Company Ltd., Nagoya, Japan). Flare values were obtained 30 minutes after pupillary dilation with 0.5% tropicamide and 5% phenylephrine hydrochloride. Five measurements were taken and averaged in each eye. The results are expressed as photon counts per millisecond (pc/ms).
Statistical Analysis
The data are presented as the arithmetic mean ± standard deviation (SD). Statistical differences between the groups were analyzed by independent-samples Student t tests. The relationship between aqueous flare values and visual parameters were examined by Spearman rank correlation coefficient. The aqueous flare values were converted to logarithmic scale to better approximate a normal distribution. All of the statistical analyses were performed with SAS software (version 9.3; SAS Institute, Cary, North Carolina, USA). P values <.05 were considered significant.
Results
Aqueous Flare Values in Retinitis Pigmentosa Patients and Control Subjects
A total of 305 eyes of the 160 patients with RP were age-matched with 101 eyes of the 59 control subjects. The demographic data of the study population are listed in Table 1 . There were no significant differences in age or sex distribution between the groups. The aqueous flare values were significantly increased in RP patients (10.6 ± 7.9 pc/ms) compared to those of the control subjects (5.0 ± 2.1 pc/ms, P < .0001; Figure 1 , Left).
Because previous studies showed that flare values increase with age in healthy subjects, we performed an age-subgroup analysis of the study population. Consistent with the previous findings, we found that the aqueous flare values increased with age in both the healthy subjects and RP patients. In addition, the aqueous flare values in the RP patients were significantly higher than those in the healthy subjects in each age subgroup (in their <30s, P = .0039; 30s, P = .0320; 40s, P = .0009; 50s, P < .0001; 60s, P = .0004; ≥70, P = .0002; Figure 1 , Right).
Correlation Between Aqueous Flare and Visual Parameters in Retinitis Pigmentosa Patients
We next investigated the correlations between aqueous flare values and visual parameters in the RP patients. Spearman rank testing showed that the aqueous flare values were significantly correlated with the VA ( r = 0.359, P < .0001) and mean deviation (MD) values ( r = −0.330, P < .0001; Figure 2 and Table 2 ). In addition, age was significantly associated with the aqueous flare values ( r = 0.414, P < .0001; Table 2 ).
| Flare | P | Eye (n) | |
|---|---|---|---|
| r | |||
| Age | 0.414 | <.0001 | 305 |
| VA (logMAR) | 0.359 | <.0001 | 305 |
| MD value (dB) | −0.330 | <.0001 | 205 |
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
