AMA series design. Copyright Oxford University Press.

1. Daniel M. Albert Mark J. Lucarelli
Another Author
Clinical Atlas of Procedures
in Ophthalmic Surgery

2. Chapter 15 Laser Photocoagulation and Photodynamic
Therapy for Retinal and Choroidal Disease
Peter J. Kertes, MD
David A. Quillen, MD

3. The Diabetic Retinopathy Study 98 Chapter 13 Histopathology of Retinal Diseases
IS
OS
Rods
cones
Choroid
NFL
GCL
IPL
INL
OPL
ONL
OLM
RPE
Sclera
Retinal layers:
{
{
Sclera
Macula
Outer segmentInner segment
Rod
Cone
Spherule
Pedicle Myoid
Ellipsoid Cillium
Synaptic
body
Quillen
Figure 3
Filename: daq03b.eps
Apex
Microvilli
Choriocapillaris
Base
Schematic drawing of the nine layers of the neu-
rosensory retina, retinal pigment epithelium,
Bruch’s membrane, choroid, and sclera.
Schematic drawing of the fovea. The normal foveal de-
pression results from displacement of the inner retinal
layers including the nerve fiber layer, ganglion cell layer,
inner plexiform layer, and inner nuclear layers.
The retinal vascular endothelial cells are nonfenestrated with
tight junctions. This forms the inner blood-retinal barrier. Note
that fluorescein does not leak from normal retinal vessels.
The ratio of rods to cones is 20:1. In cones, the outer seg-
ment discs are attached to the cell membrane whereas
in rods the discs are arranged like a “stack of coins.”
Approximately 20% of individuals have a cilioretinal artery.
Cilioretinal arteries arise from the ciliary circulation and sup-
ply various portions of the peripapillary retina and macula.
The retinal pigment epithelium is a monolayer of
cuboidal-shaped cells derived from neuroectoderm.
The Diabetic Retinopathy Study
Contributor Byline
The role of laser photocoagulation in the treatment of dia-
betic retinopathy remained controversial following its first
description by Meyer-Schwickerath in the 1950s. In 1971,
the Diabetic Retinopathy Study (DRS), which was orga-
nized under the leadership of Mathew Davis, MD, began to
address these fundamental controversies definitively. The
study was the first of many well-designed, prospective, and
randomized clinical trials that guide the current practice of
ophthalmology.
Study Objectives
The question posed by the DRS was, “Does photocoagula-
tion surgery reduce the risk of severe visual loss in diabetic
retinopathy?” The DRS set out to better establish the natural
course of untreated diabetic retinopathy. It also was designed
to compare the effects of treatment techniques involving
extensive scatter photocoagulation and focal treatment of
new vessels on the surface of the retina with either xenon arc
or argon laser energy.
Treatment Groups/Trial Design
Eligible patients had diabetic retinopathy in both eyes, with
proliferative diabetic retinopathy (PDR) in at least one eye,
or severe, nonproliferative changes in both eyes. Severe non-
proliferative changes were defined as the presence of at least
three of the following:
■ cotton wool spots
■ intraretinal microvascular abnormalities (IRMAs)
■ extensive retinal hemorrhages
■ venous beading
Eligible eyes had to have a visual acuity ≥220/100 in each
eye. Eyes with a traction retinal detachment that threatened
the macula were excluded, as were eyes with a history of
previous laser photocoagulation treatment. One eye of each
participating patient was randomly selected to receive photo-
coagulation, and the fellow eye was followed independently
without photocoagulation. The mode of laser treatment was
also randomly assigned as either xenon arc or argon laser.
A total of 1727 patients were enrolled from 15 centers; 858
eyes were randomized to receive argon laser photocoagula-
tion and 869 were randomized to receive xenon arc. The
primary outcome measure was development of severe visual
loss, that is, visual acuity 5/200 at two or more consecutive
4-month follow-up visits.
Summary of Results and Implications
for Clinical Practice
The findings of the DRS mandate prompt scatter laser pho-
tocoagulation in eyes with high-risk PDR. High-risk charac-
teristics are defined as the presence of three or more of the
following:
■ vitreous or pre-retinal hemorrhage;
■ new vessel growth;
■ new vessel growth on or within 1 disc diameter (DD) of
the optic disc (NVD); or
■ severe new vessels (NVD ≥ one-fourth to one-third of a
disc area or, in the absence of NVD, an area ≥ one-half
disc area of retinal neovascularization elsewhere [NVE]).
The DRS scatter laser photocoagulation treatment proto-
col reduced the risk of severe visual loss by greater than 50%.
Ongoing follow-up of some of the original study participants
confirmed that the beneficial effects of extensive scatter pho-
tocoagulation persist for at least 15 years after treatment and
suggested that these beneficial effects are permanent.
In high-risk PDR, the benefits of photocoagulation
were clear. In eyes with severe nonproliferative diabetic
retinopathy (NPDR) or PDR without high-risk character-
istics, however, the DRS findings were not clear. They did
not provide a clear choice between prompt treatment and
care­ful follow-up with deferral of treatment until high-risk
characteristics developed. The risk of severe visual loss in
these eyes appeared to be relatively low. Subsequent analysis
of the data accumulated in the DRS found that the incidence
of severe visual loss in eyes of older-onset diabetic patients
randomized to deferral of photocoagulation exceeded that of
younger-onset diabetics. In eyes of older-onset diabetics, the
analysis suggested that laser treatment should be seriously
considered, even though these eyes may not fulfill the origi-
nal criteria for high-risk characteristics.
The DRS also found that treated eyes were more likely to
suffer an initial loss of two to four lines of visual acuity. This
loss was largely secondary to increased macular edema. As
more untreated eyes suffered significant visual loss over time,
this difference no longer existed after 1 year.
Treatment also resulted in peripheral visual field loss, an
effect that was more often seen in eyes randomized to xenon
arc treatment than in those randomized to receive argon
laser scatter photocoagulation.
selec ted references
Acute Posterior Multifocal Placoid Pigment Epitheliopathy
1. Comu S. Verstraeten T, Rinkoff JS, Busis NA. Neurological
manifestations of acute posterior multifocal placoid pigment
epitheliopathy. Stroke. 1996; 27:996–1001.
2. Gass JDM. Stereoscopic Atlas of Macular Diseases. 4th ed. St.
Louis: Mosby. Inc; 1997:688–693.
3. Park D, Schatz H, McDonald HR, Johnson RN. Indocyanine
green angiography of acute multifocal posterior placoid pigment
epitheliopathy. Ophthalmology. 1995; 102:1877–1883.

4. The Early Treatment Diabetic Retinopathy Study 1110 Chapter 13 Histopathology of Retinal Diseases
Acute branch retinal vein occlusion with flame-
shaped retinal hemorrhages and cotton wool
spots involving the nerve fiber layer.
Cystoid macular edema following cataract surgery. The
cyst-like spaces form in the outer plexiform layer of the
retina (Henle’s layer). Fluorescein angiography reveals
a classic “petaloid” pattern of hyperfluorescence.
Cherry red spot following a central retinal artery oc-
clusion. The ischemic retinal whitening occurs in the
inner retina of the macula where the ganglion cell
and nerve fiber layers are thickest. The central red spot
is a result of the normal choroidal circulation.
Commotio retinae following a blunt trauma injury. The
deep retinal whitening results from shearing of the outer
segments of the photoreceptors. Note the normal reti-
nal blood vessels overlying the retinal whitening.
Myelinated nerve fiber layer. Note the arcuate pattern of
the nerve fiber layer around the macula. The larger reti-
nal vessels are located within the nerve fiber layer.
Lipid exudate in the macula following malignant hyperten-
sion. The lipid may form a star-pattern within the middle
layers of the retina as it radiates from the center of the macula.
The Early Treatment Diabetic Retinopathy Study
keyterms diabetic, retinopathy, photocoagulation,
panretinal, macular edema
The Diabetic Retinopathy Study (DRS) clearly demonstrated
the benefits of panretinal laser photocoagulation in prolifera-
tive diabetic retinopathy (PDR) with high-risk characteristics.
The DRS did not, however, address the question of timing or
extent of panretinal laser photocoagulation in diabetic retin-
opathy. Also, it did not clarify the role of laser photocoagula-
tion in early PDR. While diabetic macular edema had been
recognized as an important source of visual loss in diabetic
retinopathy, the role of laser treatment in this setting had
yet to be verified by a randomized, controlled clinical trial.
The Early Treatment Diabetic Retinopathy Study (ETDRS)
addressed these issues. In addition, the literature of the day
was replete with papers extolling both the risks and benefits
of adjunctive aspirin use in the management of diabetic
retinopathy. The results of the ETDRS would finally settle
the issue.
Study Objectives
The ETDRS set out to answer three questions:
■ When in the course of diabetic retinopathy is it most
effective to initiate panretinal photocoagulation?
■ Is photocoagulation effective in the management of
diabetic macular edema?
■ Is aspirin treatment effective in altering the course of
diabetic retinopathy?
Treatment Groups/Trial Design
Eligible patients were diabetics with mild, moderate, or
severe nonproliferative diabetic retinopathy (NPDR) or early
PDR in both eyes. As the DRS had clearly shown the benefit
of scatter laser photocoagulation in eyes with high-risk PDR,
such patients were excluded from the ETDRS.
The ETDRS defined macular edema as thickening of the
retina and/or hard exudates within 1 disc diameter (DD)
of the center of the macula. Clinically significant macular
edema (CSME) was defined as the presence of one or more
of the following:
■ retinal thickening at or within 500 μm of the center of the
macula;
■ hard exudates at or within 500 μm of the center of the
macula, if associated with adjacent retinal thickening; or
■ a zone or zones of retinal thickening 1 disc area in size,
at least part of which is within 1 DD of the center of the
fovea.
Eyes were stratified into three different categories and ran-
domized accordingly:
1. Eyes with moderate to seyere NPDR or early PDR and no
macular edema were assigned randomly to either early
photocoagulation or deferral of photocoagulation until
high-risk characteristics appeared. Those assigned to
early photocoagulation were further randomized to either
■ immediate full scatter panretinal photocoagulation or
■ immediate mild scatter panretinal photocoagulation.
2. Eyes with macular edema and “less severe” retinopathy
were assigned randomly to either early photocoagulation
or deferral of photocoagulation. Those assigned to early
photocoagulation were further randomized to one of the
following four groups:
■ immediate focal photocoagulation with deferral of
mild scatter panretinal photocoagulation until severe
NPDR develops;
■ immediate focal photocoagulation with deferral of full
scatter panretinal photocoagulation;
■ immediate mild scatter panretinal photocoagulation
with deferral of focal photocoagulation for (at least)
4 months, and focal treatment given only if CSME is
present; or
■ immediate full scatter panretinal photocoagulation
with deferral of focal photocoagulation.
3. Eyes with macular edema and “more severe” retinopathy
were assigned randomly to either early photocoagulation
or deferral of photocoagulation. Those assigned to early
photocoagulation were further randomized to one of
these four groups:
■ immediate mild scatter panretinal photocoagulation
with immediate focal photocoagulation;
■ immediate mild scatter panretinal photocoagulation
with deferral of focal photocoagulation;
■ immediate full scatter panretinal photocoagulation
with immediate focal photocoagulation; or
■ immediate full scatter panretinal photocoagulation
with deferral of focal photocoagulation.
Further randomization of patients to either aspirin
(650 mg daily) or placebo in a double-masked manner at
enrollment resulted in approximately one half of the patients
in each group receiving aspirin.
A total of 3928 study patients were enrolled at 23 clinical
centers between April 1980 and August 1985.
Outcome Measures
Outcome measures to assess the benefits of early photo-
coagulation were severe visual loss (visual acuity 5/200 at
two consecutive follow-up visits) and vitrectomy rate. The
outcome measure to assess the effect of photocoagulation on
macular edema was moderate visual loss (loss of 15 or more
letters).

5. 18 Chapter 1 Eyelids
IV. Management/treatment
A. Treatment is usually not necessary (Table 2-1).
B. Management:
1. Reduction of precipitating factors.
2. Manually pulling the eyelid may improve the
symptoms.
B. Botulinum Toxin (Botox) Injections.
1. For severe cases or cases with oscillopsia.
Blepharospasm
I. Clinical features
A. Clinical description
1. Benign essential blepharospasm (BEB) is a form of
focal dystonia with involuntary contractions of the
eyelid protractors (orbicularis oculi).
B. Signs and symptoms.
1. Uncontrolled forcible closure of eyelids (Figure 1-17)
a. Increased blinking due to irritation or foreign body
sensation
b. Bilateral involvement in approximately 80% of cases
(1) Usually exacerbated by bright light.
(2) Chronic in nature, may progressively worsen.
II. Basics
A. Pathogenesis.
1. Unknown.
2. Abnormal function of the basal ganglia of the brain.
B. Epidemiology.
1. Prevalence is 5 per 100,000
2. Symptoms occur most frequently in patients 50 to 60
years of age.
3. Female predominance: female/male ratio 2:1.
Table 2-1 Classification of Xerophthalmia*
XN night blindness
X1A conjunctival xerosis
X1B Bitot’s spots
X2 corneal xerosis
X3A corneal ulcerations/keratomalacia less than ⅓ of
the corneal surface
X3B corneal ulcerations/keratomalacia greater than ⅓
of the corneal surface
XS corneal scar
XF xerophthalamic fundus
*Adapted from Control of Vitamin A Deficiency in Xerophthalmia.
Report of a Joint World Health Organization, United States Agency
for International Development, United Nations Children’s Energency
Fund, HKI, IVACG meeting Geneva, 1982.
III. Diagnosis
A. Based on clinical evaluation.
B. Differential diagnosis.
1. Ptosis.
2. Hemifacial Spasm - affect one side of the face.
3. Meige’s syndrome - oral facial dystonia.
4. Secondary blepharospasm, related to acute stroke,
multiple sclerosis.
IV. Management/treatment
A. Medical therapy.
1. Medical therapy to treat mild cases through the use
of medicine such as diazepam, levodopa, lithium and
methyldopa.
2. Supportive treatments include stress management,
dark glasses.
B. Botulinum Toxin (Botox) Injections.
1.The most effective treatment for rapid but temporary
relive of symptoms.
2. Most patients require repeat treatment every 3 months.
C. Surgical therapy.
1. Surgical procedures are not often used to treat BEB.
2. Protractor Myectomy: resection and removal of
muscles in the upper eyelid responsible for eyelid
closure.
3. Neurectomy: resection and removal of the small facial
branches of the orbicularis muscles.
Eyelid Myokymia
I. Clinical features
A. Synonyms.
1. Lid twitching.
B. Clinical description.
1. Spontaneous fine contractions of the orbiculars oculi
muscles. Mostly affect the lower lids. It is a benign,
self-limited condition.
C. Signs and symptoms.
1. Sporadic “twitching” or “jumping” of one of the lower
eyelids. The upper lids can also be affected.
2. Most of cases are unilateral involvement.
3. May occur intermittently for days to months.
II. Basics
A. Pathogenesis.
1. Unknown
2. Irritation of the nerve fibers within the muscle.
B. Precipitating Factors:
1. Stress.
2. Fatigue.
3. Excessive caffeine or alcohol intake.
Abnormalities of eyelid position/formation continued