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1088 RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES 2016 VOLUME 36 NUMBER 6
Fig. 2. Right angle vessels on ultra-WF fluorescein angiography. A. Terminal networks and microaneurysms are often seen adjacent to these vessels. B.
Right angle vessels (blue arrows) turn away from areas of far peripheral capillary nonperfusion. C. A more extreme example of a right angle vessel (blue
arrows) that turns back in the direction from which it originated. Orange arrows highlight peripheral drusen.
diagnosis, and known hypertensive status are listed in more of these changes were noted in most study eyes
Table 1. (P , 0.01).
The mean peripheral arterial filling time (from the Subgroup analysis was performed to determine the
start of arterial phase to completion of peripheral difference in the proportion of peripheral findings across
arterial filling) was 8.65 ± 2.54 seconds (range: 3–15 different groups. This was first performed based on
seconds). Arteriovenous shunting was not seen in the ophthalmic diagnosis (Table 4). We further divided the
periphery of any study eye (Table 2). Vessels cross- groups based on the presence or absence of systemic
ing the horizontal raphe (Figure 1) were present in hypertension and age (.65 or #65) (Table 4). In the
44.83% of eyes. Peripheral vascular changes, such as hypertensive group, there was a smaller proportion that
right angle vessels (Figure 2) and terminal networks had right angle vessels (P , 0.01) and terminal networks
(Figure 3) were noted in 70.69% and 77.59% of eyes (P , 0.01). For those .65 years, there were a smaller
respectively, and were more likely to be present proportion of patients with right angle vessels (P ,
than not (P , 0.01) (Table 2). 0.05) and ground glass hyperfluorescence (P , 0.01).
Additional peripheral findings included areas absent
of capillary detail (Figure 4) in 98.28%, ground glass Discussion
hyperfluorescence (Figure 5) in 87.93%, peripheral
drusen (Figure 6A) in 34.48%, and microaneurysms As experience with WF grows, so does awareness of
(Figure 6B) in 41.38% (Table 3). Surprisingly, one or peripheral findings in a broad range of retinal
Fig. 3. Terminal networks on ultra-WF fluorescein angiography. A. These networks frequently have associated microaneurysms (blue arrow). B. They are often
seen adjacent to an area of peripheral capillary nonperfusion. C. The magnified, inverted image highlights the branched pattern of capillaries within the networks.
1090 RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES 2016 VOLUME 36 NUMBER 6
pathologies. Paradoxically, there is little descriptive included our study suggests the normal range using 2
information available regarding peripheral features in SDs is approximately between 4 seconds and 14
normal eyes. Orlin et al11 described a set of 33 control seconds. Moreover, the conventional notion is that
eyes in their study of white without pressure, but many retinal vessels typically respect the horizontal raphe.
of those controls had conditions (uveitis, vein occlu- Although this is generally the case for the postequa-
sions, and myopia) with known associated peripheral torial retinal vasculature, approximately 45% of eyes
changes. Kaneko et al9 evaluated eyes with pathologic in the current series had vessels crossing the hori-
myopia as compared with 42 emmetropic eyes from zontal raphe peripherally.
a population of patients with age-related macular Several of the other vascular architectural findings
degeneration or central serous chorioretinopathy. noted in this study are unique to the normal retinal
However recent studies have suggested that there are periphery. A sharp, right angle vascular course was
peripheral findings in these disease processes that may noted commonly. Terminal networks are also common
limit their usefulness as normals.4,5 Nonetheless, some in the far periphery and are best appreciated approx-
of their findings relating to microaneurysms, periph- imately 60 seconds into the angiogram. We suspect
eral avascular areas, and retinal vascular changes do these areas mark a watershed zone in circulation; thus,
mirror our findings. they may reflect an area of overall reduced perfusion.
Our baseline findings of the peripheral vascular The prevalence of missing capillary details and
architecture challenge some common assumptions in presence of ground glass hyperfluorescence were high
vascular anatomy. For instance, arterial phase filling is in study eyes. This pattern was noted for its prominent
classically taught as lasting approximately 2 seconds; appearance in the periphery, yet its significance in
however, when the peripheral arterial circulation is normal patients and pathologic conditions is not well
established. This pattern of peripheral change is hypertensive population we examined was partially,
similar to the “Pattern two” as described by Orlin if not completely, controlled. Future large-scale stud-
et al11 when evaluating patients with white without ies are warranted to determine the clinical significance
pressure. We entertained the possibility this might of far peripheral microaneurysms and drusen. Differ-
have been an artifactual finding, perhaps a consequence entiating the two findings may be challenging. The
of a shadowing effect of the imaging system. Yet, vascular association of the microaneurysms aside, dru-
closer evaluation of the vessels passing through the sen are distinguished by the fact that they are both
areas of absent capillary detail reveals no commensu- independent of the vasculature and generally demon-
rate dimming, as one would expect from a shadowing strate brighter fluorescence when in the far periphery.
artifact. It remains unclear whether these areas lack There are several limitations of this study. First, it is
capillary detail because of capillary 1) nonformation a retrospective study with the inherent biases known to
or 2) a secondary loss of capillaries. The latter case such reviews. Second, we used a surrogate for normal
would more classically be defined as capillary nonper- eyes when evaluating the periphery. However, absent
fusion. We hypothesize that the ground glass hyper- exposing asymptomatic patients with normal emme-
fluorescence may reflect areas of peripheral retinal tropic eyes to the risks of fluorescein angiography
pigment epithelium thinning, resulting in greater trans- there is likely no better alternative. Third, one variable
mission of subjacent choroidal hyperfluorescence.12 we could not account for because of unavailable A-
Microaneurysms and peripheral drusen were also scan measurements was degree of myopia in pseudo-
noted commonly in our patient cohort. The hypothesis phakic eyes. However, as there is no known evidence
that these findings would increase with age or with of increased myopia in patients with ERM and
hypertensive status was not confirmed in subgroup choroidal nevi, one would expect a relatively normal
analysis. One possibility is that hypertensive patients distribution of refractive errors in our study cohort.
were identified based on medical history or use of Fourth, ERM can often have secondary changes on
a hypertensive medication—thus ensuring that the central retinal vasculature because of tractional
forces. These tractional forces may alter the tortu-
osity of peripheral retinal vasculature causing right
Table 3. Peripheral Findings angle vessels or altering the number of vessels
Category Number Percentage crossing the horizontal raphe as reported; but this
does not seem to be the case as the frequency of
Capillary nonperfusion Present 57 98.28
Absent 1 1.72 these findings by diagnoses (i.e., ERM vs. Nevus)
Ground glass Present 51 87.93 seems to be similar. Moreover, it is less likely that
hyperfluorescence Absent 7 12.07 tractional changes alter the development of the other
Microaneurysms Present 24 41.38 factors examined (i.e., terminal networks, capillary
Absent 34 58.62 nonperfusion, ground glass hyperfluorescence, mi-
Peripheral drusen Present 20 34.48
Absent 38 65.52 croaneurysms, and peripheral drusen). Future studies
would likely benefit from including measurements of
1092 RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES 2016 VOLUME 36 NUMBER 6
refractive status and axial length. Last, our study patients with familial exudative vitreoretinopathy. Ophthalmol-
population was not large enough to allow for broad ogy 2014;121:262–268.
3. Hong BK, Nazari Khanamiri H, Rao NA. Role of ultra-
statements regarding population-based findings. widefield fluorescein angiography in the management of uve-
In summary, we describe peripheral fundus features itis. Can J Ophthalmol 2013;48:489–493.
and angiographic findings in eyes of patients with 4. Tan CS, Heussen F, Sadda SR. Peripheral autofluorescence
choroidal nevi and ERM, who would be presumed to and clinical findings in neovascular and non-neovascular age-
have an otherwise normal retinal periphery. Unique related macular degeneration. Ophthalmology 2013;120:
1271–1277.
aspects of the peripheral retinal vasculature were noted 5. Pang CE, Shah VP, Sarraf D, Freund KB. Ultra-widefield
with moderate prevalence. Additionally, peripheral imaging with autofluorescence and indocyanine green angiog-
areas with absent capillary details are far more raphy in central serous chorioretinopathy. Am J Ophthalmol
common than one might initially suspect. These 2014;158:362–371 e2.
findings may provide a reference point for studies 6. Shah SP, Jain A, Coffee RE, McCannel TA. Optos Panoramic
200MA ultrawide-field imaging of peripheral RPE adenoma.
addressing pathologies with peripheral retinal vascular Semin Ophthalmol 2009;24:37–39.
findings. 7. Kernt M, Pinter F, Hadi I, et al. Diabetic retinopathy: compar-
Key words: fluorescein angiography, peripheral ret- ison of the diagnostic features of ultra-widefield scanning laser
ophthalmoscopy Optomap with ETDRS 7-field fundus photog-
ina, retinal imaging, widefield imaging. raphy. Ophthalmologe 2011;108:117–123.
8. Patel RD, Messner LV, Teitelbaum B, et al. Characterization of
ischemic index using ultra-widefield fluorescein angiography
Acknowledgments in patients with focal and diffuse recalcitrant diabetic macular
edema. Am J Ophthalmol 2013;155:1038–1044.
A. Capone had full access to all of the data in the 9. Kaneko Y, Moriyama M, Hirahara S, et al. Areas of nonper-
study and takes responsibility for the integrity of the fusion in peripheral retina of eyes with pathologic myopia
data and the accuracy of the data analysis. detected by ultra-widefield fluorescein angiography. Invest
Ophthalmol Vis Sci 2014;55:1432–1439.
10. Yannuzzi LA, Rohrer KT, Tindel LJ, et al. Fluorescein angiog-
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