CLINICAL SCIENCES The Microperimetry of Resolved Cotton-Wool Spots in Eyes of Patients With Hypertension and Diabetes Mellitus Jae Suk Kim, MD; Anjali S. Maheshwary, MD; Dirk-Uwe G. Bartsch, PhD; Lingyun Cheng, MD; Maria Laura Gomez, MD; Kathrin Hartmann, MD; William R. Freeman, MD Background: Retinal cotton-wool spots (CWSs) are an were imaged. The mean (SD) sensitivity of resolved CWSs important manifestation of retinovascular disease in hy- in the eyes of patients with HTN and DM was 11.67 (3.88) pertension (HTN) and diabetes mellitus (DM). Conven- dB and 7.21 (5.48) dB, respectively. For adjacent con- tional automated perimetry data have suggested relative trol areas in the eyes of patients with HTN and DM, the scotomas in resolved CWSs; however, this has not been mean (SD) sensitivity was 14.00 (2.89) dB and 11.80 well delineated using microperimetry. This study evalu- (3.45) dB, respectively. Retinal sensitivity was signifi- ates the retinal sensitivity in documented resolved CWSs cantly lower in areas of resolved CWSs than in the sur- using microperimetry. rounding controls for patients with HTN (P=.01) and those with DM (PϽ.001). Scotomas in patients with DM Methods: Retinal CWSs that resolved after 10 to 119 were denser than those of patients with HTN (PϽ.05). months (median, 51 months) and normal control areas were photographed to document baseline lesions. Eye- Conclusions: Cotton-wool spots in patients with DM and tracking, image-stabilized microperimetry with simulta- HTN leave permanent relative scotomas detected by mi- neous scanning laser ophthalmoscopy was performed over croperimetry. Scotomas are denser in eyes of patients with resolved CWSs, adjacent uninvolved areas near the lesion, DM than in those with HTN. In addition, among patients and in location-matched normal patients (age-matched). with DM, adjacent retinas not involved with CWSs have lower retinal sensitivity than in age-matched controls. Results: A total of 16 eyes in patients with DM or HTN (34 resolved CWSs) and 16 normal control eyes (34 areas) Arch Ophthalmol. 2011;129(7):879-884 HE COTTON-WOOL SPOT site of these resolved CWSs as well as stud- (CWS) is a commonly en- ies that suggest that signal transmission countered retinal lesion. failures occur in the ganglion cell axons These yellowish white areas that pass through these regions.6,7 are associated with mul- Previously, our group has shown that Ttiple disease processes but are most com- an acute CWS on time-domain and spec- monly found in patients with diabetes tral-domain optical coherence tomogra- mellitus (DM) and hypertension (HTN).1-3 phy (OCT) is hyperreflective in the inner Although controversial, the CWS has been retina with a dramatically increased aver- shown to be a localized accumulation of age decibel reflectivity.8-10 As the lesions axoplasmic debris found in the retinal resolve, a slightly hyperreflective nodular nerve fiber layer. This debris results from area can be identified at the sites of the interruptions of organelle transport in gan- lesions for up to 3 months from the time glion cell axons. There are many factors they were identified. With time, the Author Affiliations: that can cause focal interruption of axo- reflectivity of the inner retina in the area Departments of Ophthalmology, nal flow; however, clinically the common- of the CWS become closer to normal.9,10 Jacobs Retina Center at Shiley est cause is ischemia. An alternative theory The CWS-induced destruction of the Eye Center, University of suggests that CWSs are merely sentinels nerve fiber layer leads to a small focal California, San Diego, La Jolla 4,5 (Drs Kim, Maheshwary, Bartsch, of retinal nerve fiber layer disease. Clini- defect in the area of the CWS as well as Cheng, Gomez, Hartmann, and cally, CWSs disappear in 4 to 12 weeks and damages the axons of the more periph- Freeman), and Sanggye Paik for the most part are asymptomatic. How- eral ganglion cells. This can result in an Hospital, Inje University, Seoul, ever, there have been reports that de- additional, more diffuse defect in retinal South Korea (Dr Kim). scribe the development of scotomas at the sensitivity.8 ARCH OPHTHALMOL / VOL 129 (NO. 7), JULY 2011 WWW.ARCHOPHTHALMOL.COM 879 ©2011 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/24/2021 Figure 1. The custom “9-4” pattern that we used to test cotton-wool spots is illustrated. The lesion is placed at the center. All points are Goldman III size, the duration is 150 milliseconds, and a stepladder intensity change (4-2 strategy) is used. The 4 peripheral test spots are 950 µm from the center and are used as control areas. Microperimetry has become a common way to mea- METHODS sure macular function and assess the natural history and treatment outcome in macular disease. Micrope- rimetry incorporates an eye tracker, allows automated This study evaluated 12 patients identified as having CWSs from follow-up examination at the same retinal loci, and is 1999 through 2009. Six of the patients had HTN, and 6 of the combined with a color fundus camera for image regis- patients had DM. One of the patients had both HTN and DM, but fluorescein angiography changes were predominantly diabetic; tration. It has become an important tool in gathering thus, this patient was classified as having a diabetic CWS. None data about retinal function in patients with a variety of of these patients had other concurrent ocular disease that could 11 diseases. affect vision. The mean (SD) hemoglobin level of our patients Our purpose in this study was to evaluate retinal was 12.44 (1.78) g/dL (124.4 [17.8] g/L). There was no history sensitivity using microperimetry after documented of sleep apnea in any patient. We also recruited 9 patients (16 CWS regression in patients with HTN or DM. Since it eyes) who were used as matched normal patients without reti- has been shown that permanent structural changes nal disease or systemic HTN or DM. Overall, 34 lesions and the can be imaged with OCT after resolution of these surrounding retinas were evaluated with the microperimeter. lesions, it seems logical that retinal function, as might Microperimetry testing provides a subjective measure of a be measured by microperimetric sensitivity, may be patient’s visual function in a relatively small area of their retina (10°-20°). With the use of the Spectral OCT scanning laser oph- abnormal as well. Detection of retinal damage from thalmoscope (SLO) combination imaging system (OPKO In- these lesions may allow understanding of why patients strumentation, Miami, Florida), providing confocal fundus im- with a seemingly normal fundus examination have per- ages for alignment, orientation, and registration, the map sistent scotomas and decreased acuity in 2 commonly produced by this testing modality allows the operator to know encountered diseases. precisely what fundus location is being stimulated. ARCH OPHTHALMOL / VOL 129 (NO. 7), JULY 2011 WWW.ARCHOPHTHALMOL.COM 880 ©2011 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/24/2021 During a microperimetry test, a patient is shown visual in 16 eyes of 9 patients. For each CWS in the study popu- stimuli at specific light intensities at specific locations on his lation we chose 1 age- and location-matched area in nor- or her retina. The patient uses a handheld button/clicker to no- mal patients as controls. tify the system if the stimulus is seen. That feedback (or lack Microperimetric sensitivity showed that the mean (SD) thereof) determines the next intensity of the subsequent stimu- sensitivity of HTN CWSs was 11.67 (3.88) dB. The mean lus. This process is repeated for all of the stimuli in a prede- termined pattern and predetermined area. At the end of the test sensitivity of surrounding controls from HTN CWSs was the operator is given a fundus image with the stimulus pattern 14.00 (2.89) dB (Figure 3). The mean sensitivity of age- overlaid showing the dimmest intensity at which each stimu- and location-matched normal controls was 13.33 (3.27) lus was seen by the patient. The intensity level of the stimulus dB. Sensitivity of HTN CWSs was statistically different is displayed in decibels. from the surrounding control area (P=.01), but not from We designed a custom pattern of 13 test points, which we age- and location-matched normal control regions term the 9-4 pattern (Figure 1). This was designed to have sym- (P=.26). There was no significant difference between the metrical group of 9 test spots to be used in the area of resolved surrounding control in the hypertensive eyes and that of CWSs surrounded by 4 adjoining points that were 950 µm from the age- and location-matched normal eyes (P=.64). the center of grid, which we used as controls for uninvolved retina. Microperimetric sensitivity showed that the mean (SD) We chose a Goldmann III spot size with at starting stimulus of 10 dB and 150 milliseconds’ duration. These parameters al- sensitivity of DM CWSs was 7.21 (5.48) dB. The mean lowed for detection of the lesion without triggering eye move- sensitivity of surrounding control areas from DM CWSs ments. The use of the 9-4 pattern resulted in a short test time was 11.80 (3.45) dB (Figure 3). The mean sensitivity of and helped eliminate patient fatigue. Our goal was to determine age- and location-matched normal control regions was retinal sensitivity but to avoid patient fatigue. We therefore used 15.28 (2.45) dB (Figure 4). Among patients with DM, a 4-2 strategy as recommended by Convento and Barbaro.12 The fixation target was a white cross.