Ординатура / Офтальмология / Английские материалы / Oxford American Handbook of Ophthalmology_Tsai, Denniston, Murray_2011

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Photodynamic therapy (PDT)

Photodynamic therapy describes the laser stimulation of a photoactivated dye that results in the production of free radicals and the occlusion of choroidal neovascular membranes (CNV). The aim of this technique is to selectively destroy the membrane while minimizing damage to the retina above or to the RPE and to choroid below.

The most common indication is AMD, but it may be used for other choroidal neovascular membranes (e.g., in myopia, inflammatory membranes).

Mechanism

Verteporfin is a photoactivated dye that binds to lipoproteins and becomes concentrated in the proliferating vascular bed of the CNV. Laser light of 689 nm wavelength is directed onto the CNV, thereby activating the dye.

The energy level used (600 mW/cm2 x 83 sec = 50 J/cm2) is too low to cause thermal damage but is sufficient to activate the dye, which catalyses the formation of the free-radical “singlet oxygen.” This causes local endothelial cell death and occlusion of the blood supply to the CNV.

PDT in practice

In advance

Discuss with the patient the procedure and obtain informed consent. Explain its purpose (to slow progression of disease) and risks and the practicalities, such as what protective clothing to wear (Box 13.1).

On day of procedure

•Calculate spot size (greatest linear diameter + 1000 μm).

•Confirm informed consent—purpose, risks (Box 13.1).

•Ensure safety precautions (hat, long sleeves, resuscitation equipment is available).

•Insert IV cannula in a large vein (e.g., antecubital fossa).

•Reconstitute 15 mg powder with 7 mL water for injections to produce a 2 mg/mL solution, then dilute requisite dose (6 mg/m2 body surface area) with glucose 5% to a final volume of 30 mL and give over 10 min.

•At 15 min since start of infusion, start 83 sec of laser (689 nm, variable spot size, 600 mW/cm2).

Follow-up

Review with FA at 12 weeks. If recurrent leakage occurs, PDT may be performed up to 4 times/year. If severe dVA of 4 lines occurs within 1 week of treatment do not retreat unless VA returns to a pretreatment level.

Evidence for PDT in subfoveal CNV due to AMD

Predominantly classic CNV (include classic with no occult)

Treatment benefit demonstrated in the TAP (Treatment of AMD with Photodynamic therapy) study is as follows:

•TAP1: fewer than 15 letters lost in 67% vs. 39% at 1 year (p < 0.001)

•TAP2: fewer than 15 letters lost in 59% vs. 31% at 2 years (p < 0.001)

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PHOTODYNAMIC THERAPY (PDT) 417

Minimally classic CNV

There is emerging evidence for treatment benefit in those cases where there is documented progression of lesion (ilesion size on FA or dVA).

100% occult CNV

Treatment benefit demonstrated (mainly for small lesions or worse VA) in the VIP (Verteporfin in Photodynamic therapy) study was overall. The TAP study showed a trend toward benefit.

•VIP2: fewer than 15 letters lost in 45% vs. 32% at 1 year (p = 0.03); subgroup analysis suggests that the main benefit is for smaller lesions (<4 disc areas) or worse VA (<20/50).

•TAP2: fewer than 15 letters lost in 56% vs. 30% at 2 years (p = 0.06)

Evidence for PDT in subfoveal CNV due to myopia

Treatment benefit was overall; most lesions were predominantly classic. It is unclear whether there is benefit for minimally classic or occult lesions.

• VIP1: fewer than 8 letters lost in 72% vs. 44% at 1 year (p < 0.01)

Box 13.1 Patient advice regarding PDT

Side effects

•Injection-site reactions: inflammation, leakage, hypersensitivity

•Back pain: 2%

•Transient visual disturbances

•Significant visual loss: up to 4%

Contraindications

•Liver failure

•Porphyria

•Allergy to any of the components

Advice to patient

For 48 hours post-PDT, avoid direct sunlight and bright lights (including solaria, halogen, or strip-lights and undraped windows). If it is necessary to go outside during daylight hours (e.g., returning from PDT clinic), wear a wide-brimmed hat, sunglasses, long-sleeved shirt, trousers, and socks.

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Table 13.2 An approach to assessing diabetic eye disease

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DIABETIC EYE DISEASE: MANAGEMENT 423

Diabetic eye disease: management

Optimal diabetic care (Table 13.4) can best be achieved by a multidisciplinary approach. This includes doctors (PCP, endocrinologist, and appropriate specialists according to need), specialist nurses, podiatrists, ophthalmologists, and others. Education to encourage the patient in selfmanagement is critical.

Treatment—ophthalmic

Table 13.4 An approach to diabetic eye disease

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Treatment—general

Glycemic control

•Aim for an HbA1c 6.5–7%.

•For type I disease, insulin regimens include 1) twice-daily premixed insulins, 2) ultrafast or soluble insulins with each meal and long-acting insulin at night (see Table 13.5).

•For type II disease, start with diet, followed by metformin and then a sulfonylurea (e.g., glipizide or glyburide); a glitazone (e.g., rosiglitazone) may be used as an alternative to either of these; insulin may be required.

Blood pressure control

•Aim for BP <130/80 or <125/75 if there is proteinuria.

•Effective antihypertensives include angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor (AIIR) antagonists, B-blockers, and thiazide diuretics.

Cholesterol control

•Aim for lipid lowering if there is >30% 10-year risk of coronary heart disease (current recommendations, although ideally, treat all with risk >15%). This can be calculated from the Framingham equation.

•A statin is the drug of choice; fibrates may be helpful if iTG and dHDL.

Support renal function

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DIABETIC EYE DISEASE: SCREENING 425

Diabetic eye disease: screening

What is screening?

Screening is the systematic testing of a population (or subgroup) for signs of asymptomatic or ignored disease.

Screening for diabetic eye disease

The classification systems for diabetic retinopathy range from the very detailed Arlie House system (generally for use in trials) to the dichotomous nonproliferative vs. proliferative division. In terms of clinical management, the commonly used preproliferative (mild, moderate, severe) and proliferative grading is familiar and has been adopted by practicing ophthalmologists and retina specialists.

Although screening may be performed by dilated funduscopy, quality assurance can be more readily achieved when there is a photographic record. Hence, a regional program of diabetic retinopathy telemedicine screening is recommended. Digital photography could be performed in mobile clinics, in selected primary or secondary care clinics, or by community optometrists and ophthalmologists. Grading of the photographs could be performed by the same clinics or the photographs could be sent to an approved reading center.

Patients with evidence of disease are referred to a local vitreoretinal specialist for treatment and/or further evaluation (Table 13.6).

Table 13.6 Management recommendations for patients with diabetes