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Retinal Vascular Disease: Diabetic Retinopath

y
Hikban Fiqhi K.
Proliferative Diabetic
Retinopathy
• As retinopathy progresses, capillary damage and nonperfusion
increase.
release of vasoproliferative factors
Worsening retinal
leads
ischemia to ...
subsequent development of
retinal neovascularization

One of the major proangiogenic factors isolated

VEGF from the vitreous of patients with PDR

Stimulate neovascularization of the retina, optic nerve head, or anterior segment

 Extraretinal fibrovascular proliferation, which defines
PDR, progresses through 3 stages:

1. Fine new vessels with minimal fibrous tissue cross and extend
beyond the ILM

2. The new vessels increase in size and extent,

developing an increased fibrous component.

3. The new vessels regress, leaving residual fibrovascular tissue

 on or within a disc diameter of the
disc (NVD, neovascularization of the
Neovascular disc)
categorized by its
proliferation location ...
elsewhere (NVE, neovascularization
elsewhere)

Patients may receive treatment at any stage of PDR;

however, treatment is usually considered mandatory once an
eye has developed high-risk characteristics.
 PDR with high-risk characteristics is defined as
having any of the following findings:
• any NVD with vitreous or preretinal hemorrhage

• extent of NVD greater than or equal to one-fourth disc

area, with or without vitreous or preretinal hemorrhage
(≥ ETDRS standard photograph 10A)

• extent of NVE greater than or equal to one-half disc

area, with vitreous or preretinal hemorrhage
Fundus photograph of a left eye
demonstrates neovascularization
of the disc (NVD, arrow) with a
small amount of vitreous hemo-
rrhage. Even without vitreous he-
morrhage, this degree of NVD is
the lower limit of moderate NVD
and is considered high-risk PDR.
Fundus photograph of a right
eye shows cotton-wool spots
and moderate neovasculari-
zation elsewhere (NVE) with
preretinal hemorrhage.
Management of Proliferative Diabetic
Retinopathy and Its Complications

GOAL:
to control ischemia and reduce ocular VEGF levels
so that neovascularization can involute or regress.

This management can be accomplished with intravitreal adminis-

tration of anti-VEGF drugs or with ablation of ischemic retina via
laser photocoagulation.
Because of the contraction of fibrovascular
tissue, treatment may be followed by:
• increased vitreoretinal traction
• recurring vitreous hemorrhage
• tractional retinal detachment
• and/or combined tractional and rhegmatogenous retinal detachment.

Complications from PDR or its treatment—vitreous hemorrhage and

tractional retinal detachment—can be addressed with vitreoretinal
surgical interventions, when appropriate.
Nonsurgical management of proliferative diabetic
retinopathy → anti VEGF and steroid drugs

• Intravitreal administration of anti-VEGF drugs is highly effective at regre-

ssing retinal neovascularization in eyes with PDR.

• Anti-VEGF therapy leads to regression of diabetic neovascular complexes

in both newly diagnosed cases and chronic, refrac- tory disease.

• Potential complications → Tractional retinal detachments, retinal tears,

and combined tractional and rhegmatogenous retinal detachments that
are related to the induced rapid contracture of the fibrovascular tissue.
• Anti-VEGF therapy is a reasonable first-line treatment alternative to panretinal
photocoagulation (PRP) for many eyes with PDR.

• The DRCR.net Protocol S study randomized eyes with active PDR to treatment
with either standard-care prompt PRP or intravitreal ranibizumab and defe-
rred PRP. At 2 years, visual outcomes were equivalent between the PRP and
anti-VEGF treated groups.

• However, ranibizumab treatment was associated with multiple benefits over

PRP, including better average vision over the 2 years, reductions in peripheral
visual field loss, reduced rates of vitrectomy surgery, and fewer cases of DME
onset.
• Ranibizumab was well tolerated; no substantial differences
in rates of major cardiovascular adverse events were found
between the treatment groups.

• Longer-term follow-up through the full 5-year study duration

will determine whether anti-VEGF treatment burden decreases
over time and whether the anti-VEGF effect endures after
treatments are halted.
• Although ranibizumab is effective for PDR treatment and offers some
advantages over PRP, whether to use anti-VEGF versus PRP should be
based on individual patient circumstances.

• Patients receiving anti-VEGF need to be able to adhere to near month-

ly follow up visits throughout the first 1–2 years of treatment.

• For patients who have a high likelihood of nonadherence due to medi-

cal instability or other limitations, treatment with PRP is the most
appropriate option.
• Anti-VEGF drugs also cause involution of anterior segment
neovascularization and have been successfully used to treat
neovascular glaucoma.

• In addition, when administered preoperatively, these drugs

may be help-ful as an adjunct to vitrectomy to manage
complications of PDR.
• Although steroid agents are not used for primary treatment of
PDR, they do reduce PDR-related outcomes in diabetic eyes.

• Combined rates of vitreous hemorrhage, need for PRP, and de-

velopment of neovascularization, as viewed on fundus
photographs or during a clinical examination, are reduced in
eyes receiving intravitreal steroid therapy for non-PDR
indications, such as DME.
Surgical management of proliferative diabetic
retinopathy → Laser surgery

• The mainstay of treatment for PDR was thermal laser photocoagulation

in a panretinal pattern to induce regression of neovascularization.

• Treatment indications are still largely based on findings from the Diabetic
Retinopathy Study (DRS).

• For patients with high-risk PDR, PRP treatment in eyes not already
receiving anti-VEGF therapy is almost always recommended.

• PRP destroys ischemic retina, which produces growth factors, such as

VEGF, that promote disease progression.
• PRP increases oxygen tension in the eye via 2 mechanisms:
(1) decreasing oxygen consumption overall as a result of the purposeful
retinal destruction
(2) increasing the diffusion of oxygen from the choroid in the areas of
the photocoagulation scars.

• Collectively, these changes result in the regression of existing neovascular

tissue and prevent progressive neovascularization.
• Laser administration may be accomplished in a single session or
over multiple sessions.

• Some clinicians combine anti-VEGF therapy with PRP with the ratio-
nale that initial anti-VEGF therapy will regress neovascularization
quickly, whereas the effect of the PRP will endure over subsequent
years, without the need for long-term intravitreal injections.
• Full PRP, as used in the DRS and ETDRS, included 1200 or more 500-μm
burns using argon green or blue-green lasers, separated from each other
by one half burn width.

• Uncontrolled studies have suggested that pattern scan laser treatments

may not be equivalent in their treatment effect on a burn-for-burn
comparison; the burn-count target for equivalent treatment effect with
pattern scan laser treatment may need to be higher.
 Fundus photograph shows an
eye that has undergone
panretinal photocoagulation
(PRP) treatment. Laser scars
are characterized by either
chorio-retinal and retinal
pigment epithelium (RPE)
atrophy or RPE
hyperpigmentation.
• Adverse effects of scatter PRP:
- Choroidal detachment
- Decreases in night vision, color vision, contrast
sensitivity, and peripheral vision
- Pupillary dilation

• Some patients may experience a transient loss of 1 or 2 lines of

visual acuity or increased glare following treatment.
• Other transient adverse effects include loss of accommodation, loss of
corneal sensitivity, and photopsias. Macular edema may also be preci-
pitated or worsened by PRP.

• Heavy treatment, when necessary, should be performed in areas of the

retina where vision loss is less noticed by patients or in areas that are
associated with lower rates of morbidity.

• Great care must be taken to avoid foveal photocoagulation, especially

when using image-inverting lenses.
Management of neovascularization of the iris
or anterior chamber angle

• Small, isolated tufts of neovascularization at the pupillary border are

relatively common in eyes of patients with diabetes mellitus.

• Treatment can be withheld in eyes with these tufts in favor of careful mo-
nitoring, with relatively short intervals between slit-lamp and gonioscopic
examinations.

• Treatment usually consists of PRP; intravitreal injection of anti-VEGF

drugs can be used as a temporizing measure to reduce neovasculariza-
tion until definitive PRP is administered.
Vitrectomy surgery for complications of
diabetic retinopathy

Indications for pars plana vitrectomy in patients with PDR are:

• Nonclearing vitreous
hemorrhage
• Significant recurring vitreous hemo-
rrhage, despite use of maximal PRP
• Dense premacular subhyaloid
hemorrhage
• Tractional retinal detachment invol-
ving or threatening the macula
• Combined tractional and rhegmato-
genous retinal detachment
• Red blood cell–induced (erythroclastic)
glaucoma and “ghost cell” glaucoma
• Anterior segment neovascularization
with media opacities preventing PRP
Vitreous hemorrhage

• The Diabetic Retinopathy Vitrectomy Study (DRVS) investigated the

role of vitrectomy in the management of eyes with severe PDR.

• Benefits of early (1–6 months after onset of vitreous hemorrhage)

versus late (1 year after onset) vitrectomy were evaluated.

• Eyes of patients with type 1 diabetes mellitus and severe vitreous

hemorrhage clearly demonstrated a benefit from earlier vitrectomy,
whereas eyes of patients with type 2 or mixed diabetes did not.
• Patients with previous, well-placed, complete PRP who have vitreous
hemorrhage secondary to PDR may be observed for a longer period
prior to initiating intervention.

• Frequent echography (ultrasound) studies are necessary to monitor

for retinal detachment in patients with dense, nonclearing vitreous
hemorrhages.

• If a retinal detachment is discovered, the timing for the vitrectomy

depends upon the characteristics of the detachment.
• Patients with bilateral severe vitreous hemorrhage should undergo
vitrectomy in 1 eye as soon as possible for vision rehabilitation.

• Recent advances in vitreoretinal surgery, including smaller-gauge

instrumentation facilitating faster operating times and fewer com-
plications, have led to earlier intervention for nonclearing vitreous
hemorrhage.
Tractional retinal detachment

• Complications from PDR may be exacerbated by vitreous

attachment to and traction on fibrovascular proliferative
tissue, often causing se-condary tractional retinal
detachments.
• Partial posterior vitreous detachment frequently develops in eyes
with fibrovascular proliferation, resulting in traction on the new
vessels and vitreous or preretinal hemorrhage.
• Tractional complications may ensue:
- vitreous hemorrhage
- retinal schisis
- retinal detachment
- macular heterotopia
- progressive fibrovascular proliferation
• Contraction of the fibrovascular proliferation and vitreous may
result in retinal breaks and subsequent combined tractional and
rhegmatogenous retinal detachment.

• The presence of chronic retinal detachment in eyes with PDR con-

tributes to retinal ischemia and may account for the increased risk
of anterior segment neovascularization in such eyes.
• Tractional retinal detachment that does not involve the macula
may remain stable for many years.

• When the macula becomes involved or is threatened, prompt

vitrectomy is generally recommended.

• Combined tractional and rhegmatogenous retinal detachment

may progress rapidly; urgent surgery should be considered for
these patients.
Recommended Diabetes-Related Ophthalmic Examinations
• In the first 5 years following diagnosis of type 1 diabetes mellitus, retinopathy is
rare. By contrast, at the time of initial diagnosis of type 2 diabetes mellitus, a large
percentage of patients have established retinopathy and require concomitant
ophthalmic examination.
• Because pregnancy poses a risk of diabetic retinopathy progression, an eye
examination is recommended in the first trimester and thereafter at the discretion
of the ophthalmologist.
• The frequency of follow-up visits depends on the severity of the retinopathy,
history of blood glucose levels, and blood pressure control, as well as the threat to
visual function from potentially missed opportunities to treat
Thank you