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2.7 Treatment ofRAM
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Fig. 2.11 Fluorescein angiography (a) and indocyanine green angiography (b) of the same patient (as in Fig.2.10),
demonstrating RAM (blue arrow) in the late phase
33
2.7 Treatment ofRAM
photocoagulation of haemorrhagic RAMs,
although no difference was noted in the visual
Most RAMs, especially haemorrhagic RAMs,
undergo spontaneous involution (Fig.2.12) [3]. If
the visual acuity does not improve even after the
resolution of the RAM, it may be due to persistent hard exudates or subfoveal haemorrhage in
the macula [51].
Signicant vitreous haemorrhage, if present,
may require pars plana vitreous surgery (PPV)
for its clearance. Patients with subretinal haemorrhage may require displacement of blood by
injection of tPA and gas tamponade with PPV
(Figs. 2.13 and 2.14) [52]. Signicant visual
improvement has been noted following laser
improvement in those observed or laser-treated
exudative RAMs [53]. However, exudative
RAMs treated with laser photocoagulation carry
the risk of branch retinal artery occlusion. In
recent years, intravitreal injections of anti-VEGF
agents have been used successfully to treat
RAMs [54–56]. These agents decrease uid
leakage and exudates from the RAM and faster
vision improvement. Instead of the conventional
laser, navigated laser photocoagulation may provide a safer approach [57]. However, these strategies only buy time till there is a spontaneous
thrombosis in the RAM.

34
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2 Retinal Arteriolar Macroaneurysms (RAM)
ab c
Fig. 2.12 RAM (blue arrow) in the same patient (as in Fig.2.7) at initial presentation (a), showing spontaneous involu-
tion at 3months of follow-up (b) and 10months later (c), with a subsequent decrease in retinal oedema and exudation
Fig. 2.13 Massive preretinal, intraretinal and subretinal
haemorrhage due to RAM in a female (same as in
Fig. 2.10) at presentation (a), showing resolution after
surgical intervention by vitrectomy with tPA injection and
intraocular gas tamponade (b)

ab
cd
2.8 Pathology ofRAM
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35
Fig. 2.14 Following surgical treatment in the patient, as
in Fig.2.13, the RAM was seen in the ‘Early’ phase uorescein angiography (a) and indocyanine green angiogra-
2.8 Pathology ofRAM
phy (b), as well as in the ‘late’ phase uorescein
angiography (c) and indocyanine green angiography (d)
by outpouching and leakage of RBC and lipids.
There are areas of capillary non-perfusion and
There are very few pathological studies of
RAM.Longstanding RAMs show brous encapsulation, lipid-lled macrophages, cholesterol
clefts, and hemosiderin. The corresponding vein
shows inltration with inammatory cells. In the
beginning, the wall of RAM stains with Periodic
acid-Schiff (PAS) indicative of hyalinization and
brin deposit in the wall, which splits, followed
dilated capillaries near the RAM.Often thrombus
is found in the resolved RAM.It is a long-held
belief that the retinal arterioles do not have internal elastic lamina except for the central retinal
artery. Thus, nding fragments that stain for elastic lamina [58] or nding only a break in the wellformed internal elastic lamina of a RAM [59]
cannot be easily explained.

36
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2 Retinal Arteriolar Macroaneurysms (RAM)
2.9 RAM Versus Intracerebral
Arterial Microaneurysms
Ever since intracerebral haemorrhage was
ascribed to miliary aneurysms of the brain, the
pathogenesis of intracerebral haemorrhage has
remained controversial for nearly 150years [60].
Using a postmortem brain imaging technique
rst described by [61], Cole and Yates [62]
described intracerebral arterial microaneurysms
by X-raying 5mm thick coronal slices after perfusing the arteries of the freshly removed brains
with a barium-gelatin radiopaque dye. They
found fusiform and saccular arterial microaneurysms varying from 50 to 2000μm in 46% of the
hypertensive patients and only 7% of the gender
and age-matched normotensives. Like the RAMs
seen in the eye, most of these aneurysms were
seen in ages 65–74. Of the 20 brains seen with
massive intracerebral haemorrhage, 18 had associated intracerebral arterial aneurysms, most of
which were in the brains of hypertensive patients
[62]. Whereas the RAMs in the eye are clearly
shown to result in either exudation or intraocular
haemorrhage, the question remains whether similar aneurysms seen in the brain are incidental.
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Retinal Cotton Wool Spots
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3
3.1 Introduction
Of all the intraocular signs, the presence of cotton wool spots (CWS) is one of the most signicant, as even a single such spot indicates an
underlying systemic disease with serious import.
Cotton wool spots are dull, greyish-white swelling of the usually transparent retinal nerve bres
(RNFs). The CWS are variable in number and
oval in shape; they are about one-third disc in
size (varying from 0.1 to 0.8) and have highly
characteristic, somewhat fuzzy/feathery borders
(Figs. 3.1 and 3.2). These are most often clustered around the optic disc. It is due to the anoxic
insult to peripapillary RNF by the closure of the
radial capillary plexus. Retinal nerve bres
(RNF) are the axons of the retinal ganglion cells
and converge from all parts of the retina to the
optic nerve head, from where they exit to form
the optic nerve carrying visual impulses from the
eye to the brain. As these bres converge from
the optic disc, they are several layers thick in the
post pole and around the optic disc. Thus,
acquired opacication and swelling of the RNF
are most prominent in this area. Cotton wool
spots last for 4–6weeks and disappear, returning
the transparency of the affected retina (Fig.3.3).
The RNFs, if dead, are replaced by a glial scar.
In the past, CWS have also been called the soft
exudates to contrast them from the more common ‘hard exudates’, which arise from lipoproteinous deposits in the retina and have a shiny
yellow- white appearance with sharp borders. It
is to be noted that CWS are not exudates and
result from intracellular swelling and not extracellular exudation that is seen in hard exudates
(Fig. 3.4). CWS lead to RNF bundle defects
(Fig.3.5).
© The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023
A. Gupta et al., Ophthalmic Signs in Practice of Medicine,
https://doi.org/10.1007/978-981-99-7923-3_3
41

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3 Retinal Cotton Wool Spots
Fig. 3.1 A 17-year-old female with a two-week diminution of vision. Her blood pressure was 220/120. Fundus
showed multiple peripapillary cotton wool spots R>L
(red arrows) with few splinter haemorrhages R> L and
yellowish deposits in the macula (a, right eye; b, left eye).
Note the remarkable attenuation of the retinal arterioles
(black arrows). OCT line scan (blue lines) passing through
the cotton wool spots shows remarkable thickening of the
nerve bre layer in both eyes (c, right eye; d, left eye).
Hyperreective dots in the outer retina R>L. There is
hyperreectivity of the interdigitating and ellipsoid zones
(green arrows). Retinal architecture temporal to the foveal
centre is well maintained. (Images courtesy of Dr. Alok
Sen, Sadguru Chikitsa Netralya, Chitrakoot, MP India)
Fig. 3.2 Cotton wool spots (blue arrows), along with
retinal haemorrhages, in a patient with diabetes mellitus
and hypertension, seen as greyish-white lesions with
feathery borders often clustered around the optic disc

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43
Fig. 3.3 A 30-year-old woman presented with CRVO and
cotton wool spots in the right eye (a). Within 4weeks,
cotton wool spots and haemorrhages increased (b). She
was treated with injections of Avastin given every 4weeks.
After the rst injection, a dramatic resolution of the haemorrhages is seen, but cotton wool spots persist at 3weeks
(c) and 4months with extensive atrophy of the retina (d)
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