High quality ophthalmic care depends on the accurate assessment of ocular disease. Conventional direct ophthalmoscopy is used widely and provides good two dimensional views of the retina. However, the true nature of retinal disease is apparent only in three dimensions. In diabetic maculopathy, direct ophthalmoscopy can reveal retinal exudates, but the degree of macula oedema, which usually underlies the decision to treat by laser photocoagulation,1 is less clear. In glaucoma, the earliest damage can be seen as thinning of the retinal nerve fibre layer with increased cupping of the optic disc.2 These changes are best viewed stereoscopically. In both cases, disease of the retinal or optic nerve head will change the surface contour of the retina, either elevating or depressing the retinal surface by up to several hundred micrometres. Clearly, the objective quantification of these changes would be of immense benefit in diagnosing disease and monitoring disease progression and response to treatment.

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Summary points

• In diseases such as diabetic maculopathy and glaucoma changes in retinal structure precede visual symptoms

• Earlier detection of these changes allows early intervention and improves the prognosis

• Scanning laser ophthalmoscopes provide rapidly acquired views of the retina that enable the detection of these early changes

• Clinical studies have shown the value of these devices in the diagnosis of glaucoma and diabetic maculopathy

• The costs of these devices is falling and serious consideration should be given to their introduction into hospital based eye services

Techniques for retinal imaging

The three dimensional imaging of the retina has been facilitated by two technical developments. The first is the availability of cheap and powerful computers. The second is the production of affordable optoelectronics such as digital cameras and diode lasers. The incorporation of some of these technologies into clinical practice has been relatively straightforward and will be familiar to doctors in other specialties. For example, digitised photography of the retina has improved the detection of serious retinopathy in diabetes,3,4 and when linked to telemedicine has allowed the rapid referral of patients for treatment. This type of imaging is a progression of existing practice in that most ophthalmology departments have been using conventional (non-digital) fundus cameras to photograph the retina for many years (fig 1).

Figure 1.

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&#;Digitised fundus photograph of optic disc with advanced glaucoma

By contrast, scanning laser ophthalmoscopes5,6 offer a radically different view of eye disease since they provide three dimensional views of the retina7; potentially, they represent an important step forward in the assessment of retinal disease. The devices use laser light rather than conventional white light to image the fundus. A low powered diode laser beam scans the retinal surface to build up an image of the retina line by line, analogous to the formation of images on a television screen.5 Several variants of this scanning technology exist, each providing slightly different views of retinal structure. In tomographic scanning laser ophthalmoscopes the focal plane is adjusted to generate a series of images that span the retinal thickness and can be used to derive a topographic plot of the shape of retinal surface or optic disc cup (fig 2).

Figure 2.

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&#;Tomogram of optic disc obtained with Heidelberg retina tomograph scanning laser ophthalmoscope. A cursor line has been placed across the optic disc to plot the retinal surface

One drawback of this technique is that it gives only an indirect measure of changes within the retina.8 Other scanning laser devices have been developed to address this limitation. The scanning laser polarimeter measures the thickness of the retinal nerve fibre layer based on its birefringent properties (ability to polarise incident light).9 Plots of retinal nerve fibre layer birefringence approximate the variation in thickness of the layer around the optic disc10 (fig 3) and can be used to detect changes that are characteristic of glaucoma. Perhaps the most dramatic development has been optical coherence tomography, in which interference patterns generated from the reflection of partially coherent laser light are used to construct an optical cross section of the retina (fig 4).11,12

Figure 3.

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&#;Retardation image of normal optic disc taken with scanning laser polarimeter. Brighter pixels correspond to regions of increased retardation (increased retinal nerve fibre layer thickness). The thickest parts of the retinal nerve fibre layer are at the superior and inferior borders of the optic disc

Figure 4.

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&#;Image from optical coherence tomograph. Arrows show approximate thickness of retinal nerve fibre layer. The image has been artificially colour coded.

Diagnosing and monitoring disease

Several studies have examined the ability of these devices to detect glaucoma13&#;15and diabetic macula oedema.16 The tomographic scanning laser ophthalmoscope has been shown to detect glaucoma with high sensitivity (over 80%) and specificity (over 95%).14 These impressive statistics have been achieved without expert ophthalmic assessment and are based on the computerised analysis of retinal structure by the scanning laser ophthalmoscope. These ophthalmoscopes may therefore have a role in detection of glaucoma in primary care.

This technology may also help detect progressive disease in patients who have already had glaucoma or diabetes diagnosed. The ability to detect structural change is an important advantage since these changes usually occur before the onset of clinically detectable visual deficits such as a reduction in visual acuity or loss of visual field. The delay between the structural and visual changes reflects the redundancy of neural components that is built into the visual system. Thus, in glaucoma, it has been estimated that up to 50% of the retinal ganglion cells at any particular location can be lost before a visual field defect is detectable using currently available clinical methods.17 Consequently, if we rely on tests of visual acuity or visual field, significant retinal damage may have already occurred by the time that disease is detected, leading to a poorer visual prognosis.

Early detection also gives clinicians greater flexibility in managing patients. In glaucoma, quantification of the rate of optic disc cupping allows clinicians to estimate the onset of serious visual field loss, which can help when discussing the timing and possible outcomes of treatment. In diabetic maculopathy it may help improve targeting of focal laser treatment. These factors are important since the diseases have mild symptoms in the early stages, and treatment in the form of eye drops, laser, or surgery can have a greater effect on a patient's quality of life than the disease itself.

The other major advantage of these imaging technologies is that they require little patient interaction. This contrasts with commonly used clinical tests such as automated perimetry, which can be arduous for some elderly patients. Furthermore, it is likely that fewer laser images will be needed than visual field tests to detect progression of disease since the noise in a scanning laser ophthalmoscope image is much less than that seen in perimetric tests.18,19 Finally, these devices provide important documentation of the retina and optic disc, which can be valuable when discussing the prognosis or considering the medicolegal aspects of a case.

Implementation of laser technology

The main barrier to the use of scanning laser ophthalmoscopes is that they are expensive. In addition to the initial capital costs, they require experienced staff to operate them and need specialist maintenance. Taking images can, in some cases, be trying for the patient. The eye needs to be relatively immobile while the image is taken and, although the process is rapid for a single image (1.6 seconds for the scanning laser tomograph), three images are usually required to generate a clinically useful topographic map of the retinal surface. Indeed, a recent report of scanning laser ophthalmoscopy in an unselected patient population showed that up to 19% of patients could not provide satisfactory images.20 Patients may also be anxious about the new technology since lasers are often portrayed as powerful agents of destruction; their use as diagnostic tools requires careful explanation.

Further evidence is required to justify the widespread clinical use of scanning laser ophthalmoscopes. Given that the role of the NHS is to deliver a uniform high standard of patient care, the evidence that scanning laser ophthalmoscopes help diagnose diseases such as glaucoma and diabetic maculopathy argues for their installation in most ophthalmic units. However, in many units in the United Kingdom the appearance of the optic disc and macula is still documented by hand, which provides a poor objective record of retinal disease. The introduction of simpler techniques such as stereoscopic optic disc photography, which uses existing fundus cameras, may therefore provide the best value for money since these images have been shown to be of value in distinguishing normal from glaucomatous eyes.21 Similarly, the institution of free eye tests for people aged over 60 is probably a more useful first step than the widespread introduction of scanning laser ophthalmoscopes.22 When so many basic steps have yet to be taken in clinical assessment it may be premature to consider the large scale introduction of such advanced imaging equipment.

Despite these caveats, scanning laser ophthalmoscopy holds great promise for the diagnosis of ophthalmic disease, and it is important that we research its clinical application. In considering the benefits of this technology, we must not conclude that the relentless accrual of data always leads to improvements in patient care. Most patients want to spend as little time in clinic as possible and to receive the minimum necessary investigation and treatment. That said, if detailed topographic images can be acquired rapidly and with minimal discomfort, the wishes of both patient and clinician will be met. The cost of these devices remains a difficult issue. However, as with other electronic devices, this is likely to fall greatly over the next decade as development costs are recouped and computing and electronic costs are reduced. If these developments continue, the widespread use of laser imaging technology in routine clinical practice seems likely.

Footnotes

Funding: Welsh Office of Research and Development

Competing interests: None declared.

Laser is an abbreviation for (Light Amplification by Stimulated Emission of Radiation). The concept of ocular therapy using light was published first by Meyer-Schwickerath, who used the sunlight to treat patients with ocular melanoma in . On the other hand, many experiments on retinal damage from sunlight were performed in the late 's, but they are not published.

Laser Properties

Monochromatic, Coherent, & Collimated

Lasers have properties to produce highly monochromatic coherent beam that is collimated and has limited divergence. Monochromatic electromagnetic wave means that it has single wavelength eliminating chromatic aberration. Coherence of lasers is classified as either spatial or temporal. Spatial coherence allows precise focusing of the laser beam to widths as small as a few microns, while temporal coherence allows selection of specific monochromatic wavelengths within a single laser or a group of lasers. Practically, spatial coherence, allow extremely small burns to pathologic tissue, with minimal disturbance to surrounding normal tissue; on the other hand, temporal coherence allows treatment of specific tissue sites by selecting laser wavelengths that are preferentially absorbed by these tissue sites.

Principles of Laser Emission

Atoms are composed of a positively charged nucleus and negatively charged electrons at various energy levels. Light is composed of individual packets of energy, called photons. Electrons can jump from one orbit to another by either absorbing energy and moving to a higher level (excited state), or emitting energy and transitioning to a lower level. Such transitions can be accompanied by absorption or spontaneous emission of a photon.

&#;Stimulated Emission&#; is the interaction of an atom in the excited state with a passing photon leading to photon emission. The emitted photon by the atom in this process will have the same phase, direction of propagation, and wavelength as the &#;stimulating photon&#;. The &#;stimulating photon&#; does not lose energy during this interaction it simply causes the emission and continues on. For this stimulated emission to occur more frequently, the optical material should have more atoms in an excited state than in a lower state.

Laser System and Media

The lasering medium is contained in an optical cavity (resonator) with mirrors at both ends, which reflect the light into the cavity and thereby circulate the photons through the lasing material multiple times to efficiently stimulate emission of radiation from excited atoms. One of the mirrors is partially transmitting, thereby allowing a fraction of the laser beam to emerge. The lasing medium can be Solid (e.g, Ruby laser, neodymium-doped yttrium aluminum-garnet (Nd:YAG) ), Liquid : (e.g Fluorescent dye ) or Gas (e.g, Argon , Krypton ). Lasers can be pumped by continuous discharge lamps and by pulsed flash lamps. Laser pulse durations can vary from femtoseconds to infinity.

Laser- Tissue Interaction

Laser-tissue interactions can occur in several ways:

Photothermal (photocoagulation and photovaporization)

Photothermal effects include photocoagulation and photovaporization. In photocoagulation, absorption of light by the target tissue results in a temperature rise, which causes denaturization of proteins. Typically, argon, krypton, diode (810nm) and Frequency doubled ND:YAG lasers cause this type of effect. Photovaporization occurs when higher energy laser light is absorbed by the target tissue, resulting in vaporization of both intracellular and extracellular water. The advantage of this type of tissue response is that adjacent blood vessels are also treated, resulting in a bloodless surgical field. The carbon dioxide laser, with its wavelength in the far infrared (10,600 nm), uses this method of action.

Photochemical (photoablation and photoradiation)

Photochemical effects include photoradiation and photoablation. In photoradiation, intravenous administration of photosensitizing agent, which is taken up by the target tissue, causes sensitization of the target tissue. Exposure of this sensitized tissue to red laser light (690 nm) induces the formation of cytotoxic free radicals. Photoablation occurs when high-energy laser wavelengths in the far ultraviolet (< 350 nm) region of the spectrum and are used to break long-chain tissue polymers into smaller volatile fragments. The exposure times in the photoablation process is usually much shorter (nanoseconds) compared to photoradiation. Photodynamic therapy (PDT) is an example of photoradiation therapy while Excimer laser is a photoablative process.

Photoionizing (photodisruption)

In Photoionization high-energy light ( nm) is deposited over a short interval to target tissue, stripping electrons from the molecules of that tissue which then rapidly expands, causing an acoustic shock wave that disrupts the treated tissue. The ND:YAG laser works via a photodisruptive mechanism.

Laser Types in Retina

Argon blue-green laser (70% blue (488 nm) and 30% green(514nm))

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Absorbed selectively at retinal pigment epithelial layer (RPE), hemoglobin pigments, choriocapillaries, inner and outer nuclear layer of the retina. It coagulates tissues between the choriocapillaris and inner nuclear layer. The main adverse effects of these lasers are high intraocular scattering, macular damage in photocoagulation near the fovea, and choroidal neovascularization (if Bruch's membrane is ruptured).

Frequency-doubled Nd-YAG Laser (532 nm)

Highly absorbed by hemoglobin, melanin in retinal pigment epithelium and trabecular meshwork. It can be used either continuously or in pulsed mode.

PASCAL (Pattern Scan Laser) is one such type of laser that incorporates semi-Automated multiple pattern, short pulse, multiple shots with precise burn in very short duration using frequency-doubled Nd-YAG Laser (532 nm). It is commonly used nowadays in treatment of many retinal conditions (proliferative diabetic retinopathy, diabetic macular edema, vein occlusions etc.). It has many advantages when compared with conventional single spot laser, as it is produced at a very short duration (10-20 msec) compared to (100-200 msec) of conventional single spot one which leads to less collateral retinal damage. Other advantages include relatively stable scar size, less destructive same efficiency. It also permits the application of different patterns that gives more regular spots on retina with less duration.

Krypton red (647 nm)

Well absorbed by melanin and can pass through hemoglobin which makes it suitable for treatment of subretinal neovascular membrane. It also has low intraocular scattering with good penetration through media opacity or edematous retina and has ability to coagulate the choriocapillaries and the choroid.

Diode laser (805-810 nm)

It is well absorbed by melanin. The near to infrared spectrum (near invisible) makes it more comfortable to use due to absence of flashes of light. It has very deep penetration through the retina and choroid making it the laser of choice in treatment of Retinopathy of Prematurity (ROP) and some types of retina lesions. It is also used via trans-scleral route to treat the ciliary body in some cases of refractory glaucoma.

Laser-Tissue Absorption in the Retina

Melanin

Found mainly in the RPE (Retinal pigment epithelium) and choroid, and absorbs mainly wavelength between 400-700 nm. The longer the wavelength of light, the more the melanin is penetrated. For example, Diode laser with wavelength of 810 nm can penetrate deeply into the choroid.

Macular xanthophyll

Located in the inner and outer plexiform retinal layers. It protects the photoreceptors from short-wavelength light damage, but can be damaged by blue light which is why Argon green is preferred in macular photocoagulation over Argon blue.

Hemoglobin

Absorption varies according to oxygen saturation. It absorbs yellow, green, and blue wavelengths, but red light is absorbed poorly. Thus, macular lasers may, uncommonly, damage retinal vessels.

Laser delivery systems

Slit lamp

It is the most popular and common delivery system. Laser settings such as power, spot size and exposure time can be changed easily.

Indirect ophthalmoscope

Commonly used via a fiberoptic cable to deliver diode or argon lasers. It is ideal in the treatment of peripheral retina e.g. peripheral breaks and cases of retinopathy of prematurity. The spot size is altered by the dioptric effect of the condensing lens used. It may even vary depending on the refractive status of the eye (i.e. in hyperopic eyes the spot size will be smaller, and in myopic eyes it will be larger).

Endophotocoagulation

It delivered mainly argon green and diode lasers. Often used during retinal detachment repair following pars plana vitrectomy and extrusion of the subretinal fluid or in the surgical treatment of proliferative diabetic retinopathy.

Micropulse laser therapy

Micropulse laser describes a method of retinal laser delivery and can be applied with lasers of different wavelengths, such as 532 nm, 577 nm, or 810 nm. This type of delivery essentially divides the treatment into repeated microsecond impulses with intervals separating these where the retinal tissue is allowed to cool down. The laser power is set to a low level, and in general, the spots are not visible on the retina; the intention is to treat the retina on a subclinical basis while avoiding thermal damage to the underlying retina that can occur with conventional photocoagulation. While this type of laser therapy appears to be safe, its efficacy continues to be debated.[1]

Lenses Used for Laser Delivery

Selection of lens depend on many factors include, desired field of view, amount of magnification, area to be treated, and ophthalmologist preference. The commonly used contact lenses for panretinal and focal/grid retinal photocoagulation are listed in table 1 and 2. It is important to remember that most of the commonly used lenses magnify the image size; thus, the laser spot size on the machine must be set accordingly.

Table 1. Contact Lenses used for PRP Lens Image Magnification Laser Spot Magnification Field of View Goldmann 3-mirror 0.93x 1.08x 140­­&#; Mainster Widefield 0.68x 1.5x 118-127&#; Mainster PRP 165 0.51x 1.96x 165-180&#; Volk Quadraspheric 0.51x 1.97x 120-144&#; Volk Super Quad 160 0.50x 2.00x 160-165&#; Table 2. Contact Lenses used for Focal/Grid Lasers Lens Image Magnification Laser Spot Magnification Field of View Goldmann 3-mirror 0.93x 1.08x 140­­&#; Mainster standard 0.96x 1.05x 90-121&#; Mainster high magnification 1.25x 0.8x 75-88&#; Ocular PDT 1.6X 0.63x 1.6x 120-133&#; Volk area centralis 1.06x 0.94x 70-84&#;

Panretinal Photocoagulation for Treatment of Proliferative Diabetic Retinopathy

The Diabetic Retinopathy Study (DRS) established panretinal photocoagulation (PRP) as an effective treatment for high risk PDR which includes eyes with one of the three of the following risk factors: NVD greater than 1/3 disc area, any NVD with vitreous hemorrhage or NVE greater than half a disc area with preretinal or vitreous hemorrhage. The Early Treatment Diabetic Retinopathy Study (ETDRS) recommended careful follow-up without PRP for mild or moderate nonproliferative diabetic retinopathy. Laser settings for conventional retinal laser photocoagulation for diabetic retinopathy is typically performed with a continuous wave (cw) laser at 514 or 532 nm with exposure durations from 100 to 200 ms, spot sizes from 100 to 500 µm, and powers from 250 to 750 mW. If Patterned scanning laser is used, it typically utilizes settings of 532 nm wavelength, 200 µm spot size, 20 ms duration, and powers from 300 to 750 mW. Area of treatment reaches approximately &#; 500 micron-sized burns spaced between one half and 1 burn width apart, beginning temporally just outside the vascular arcades and 3-disc diameters temporal to the macula, and extending to or just beyond the equator. Some providers prefer to divide treatment into two or more sessions while others elect to perform treatment in a single session. On the nasal side of the fundus, burns begin about 1-disc diameter nasal to the optic disc and also extend to or just beyond the equator. However, specific regimens vary by practitioner.

Treatment of Diabetic Macular Edema with Laser Photocoagulation

The ETDRS recommended macular laser for Clinically significant macular edema (CSME) which was defined as any of the following based on stereoscopic fundus examination:

1. Retinal thickening within 500 µm of the foveal center;
2. Hard exudates within 500 µm of the foveal center associated with adjacent retinal thickening; or
3. Retinal thickening more than 1 disc area in size within 1 disc diameter from the foveal center

Focal photocoagulation is directed to microaneurysms more than 500 µm away from the foveal center. Treatment up to 300 µm from the foveal center is allowed if vision is 20/40 or worse. Grid photocoagulation is applied to areas of diffuse leakage and capillary non-perfusion on fluorescein angiography. Focal laser setting is a 50 to 100 µm spot size, 50 to 100 ms pulse duration, and power titrated to barely whiten the microaneurysm. Grid laser setting is a 50 to 200 µm spot size, 50 to 100 ms pulse duration, and power titrated to achieve mild burn intensities.

Transpupillary Thermotherapy (TTT)

A more intense, destructive modality, this is occasionally used for the treatment of choroidal melanomas, retinoblastoma, subfoveal choroidal neovascular membranes (CNVM) and other ocular tumors. TTT involves long exposures (~60 s) of a large spot (1.2&#;3 mm) at low irradiance (~10 W/cm2), using a near-infrared Diode (810 nm) laser that is thought to induce intralesional hyperthermia and subsequent vascular occlusion and lesion shrinkage.

Laser Photocoagulation in Branch and Central Retinal Vein Occlusions

In branch or central vein occlusions, retinal hypoxia occurs in the distribution of the occluded veins and may elicit a neovascular response in the affected area. Sector or panretinal photocoagulation is then the treatment of choice. It has been shown that macular grid laser photocoagulation can be used to treat persistent macular edema (> 3 months, vision worse than 20/40) resulting from branch vein occlusion with improvement of vision in some cases, although anti-vascular endothelial growth factor (anti-VEGF) intravitreal injections have become the standard of care.

Laser Photocoagulation in Age-Related Macular Degeneration and Related Diseases

Thermal Laser Photocoagulation

Before the era of intravitreal injections, thermal photocoagulation with the argon blue-green laser or krypton red was the first-line of treatment for exudative age-related macular degeneration (AMD) in cases of extrafoveal CNVM. However, treatment of subfoveal and juxtafoveal lesions usually yielded a dense scotoma with a high recurrence rates for the CNVM.

Photodynamic Therapy (PDT)

PDT is a form of selective laser therapy, leading to closure of the choroidal neovascular process and other active proliferating vessels, while leaving normal retinal tissue unharmed. It was first described to treat exudative AMD and studied in the VIP/TAP clinical trials, although the gold standard in treating exudative AMD has since become anti-VEGF therapy. [2]. It works by photoradiation mechanism in which previously hematoporphyrin derivative and currently verteporfin (Visudyne) is used as a photosensitizing agent followed by local application of light in the absorption spectrum of that agent (i.e. 689 nm). This will release free radicals that destroy endothelial cells causing closure of hyperproliferative vessels, as in an actively growing tumor, or in an area of active choroidal neovascularization. It remains a useful adjuvant therapy for other intraocular vascular disorders, as well as posterior segment neoplasms. PDT is now frequently used for cutaneous and subcutaneous tumors. Treatment with PDT should be guided by a recent fluorescein angiography or indocyanine green study. A light dose of 50 J/cm2 (full-fluence PDT), or 25 J/cm2 (half-fluence PDT) has been described for the treatment of choroidal neovascularization of various conditions, in addition to other choroidal vascular pathologies, including chronic central serous choroidopathy, polypoidal choroidal vasculopathy, as well as choroidal neoplasms, such as circumscribed choroidal hemangiomas.

Additional Resources

References

1. &#;

   Gawecki M. Micropulse Laser Treatment of Retinal Diseases. J Clin Med. Feb; 8(2): 242.

2. &#;

   Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin. Two year results of 2 randomised clinical trials&#;TAP report 2. Arch Ophthalmol ;119:198&#;207.

   Are you interested in learning more about Retinal Camera? Contact us today to secure an expert consultation!

3. Palanker DV, Blumenkranz MS, Marmor MF, Fifty years of ophthalmic laser therapy, Arch Ophthalmol.  Dec;129(12):-9. doi: 10./archophthalmol..293.
4. Retina and Vitreous, section 7. Basic and Clinical Science Course, AAO, -.
5. Lasers in Ophthalmology, Basic, Diagnostic, and Surgical Aspects : a Review, by Franz Fankhauser and Sylwia&#; Kwasniewska, .
6. Step by steps, laser in Ophthalmology,by Bikas Bahattacharyya, .
7. Daniel Palanker, PhD, www.AAO.org, comprehensive ophthalmology Lasers Basic properties , .
8. The Diabetic Retinopathy Study Research Group. Photocoagulation treatment of proliferative diabetic retinopathy. Clinical application of Diabetic Retinopathy Study (DRS) findings, DRS Report Number 8. Ophthalmology. ;88:583&#;600.
9. Early Treatment Diabetic Retinopathy Study Research Group. Early photocoagulation for diabetic retinopathy. ETDRS report number 9. Ophthalmology. ;98 (5 Suppl):766-785.
10. Muqit MM, Marcellino GR, Henson DB, Young LB, Turner GS, Stanga PE. Pascal panretinal laser ablation and regression analysis in proliferative diabetic retinopathy: Manchester Pascal Study Report 4. Eye. ;25(11):-.
11. Early Treatment Diabetic Retinopathy Study Research Group. Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Arch Ophthalmol.;103(12):-.
12. Early Treatment Diabetic Retinopathy Study Research Group. Treatment techniques and clinical guidelines for photocoagulation of diabetic macular edema. Early Treatment Diabetic Retinopathy Study Report Number 2. Ophthalmology. ;94(7):761-774.
13. T, Maurage CA, Mordon S. Transpupillary thermotherapy (TTT) with short duration laser exposures induce heat shock protein (HSP) hyperexpression on choroidoretinal layers. Lasers Surg Med. ;33(2):102-107.
14. Complications of Age-related Macular Degeneration Prevention Trial (CAPT) Research Group. Risk factors for choroidal neovascularization and geographic atrophy in the complications of age-related macular degeneration prevention trial. Ophthalmology. ;115(9):-.
15. Moo-Young GA: Lasers in opthalmology, In High-tech medicine. West J Med Dec; 143:745-750.
16. Verteporfin in Phododynamic Therapy Study Group. Verteporfin Therapy of subfoveal choroidal neovascularisation in age-related macular degeneration: Two-year results of a randomised clinical trial including lesions with occult with no classic choroidal neovascularisation&#;Verteporfin in photodynamic therapy report 2. Am J Ophthalmol ;131:541&#;60.
17. TAP study group. Photodynamic therapy of subfoveal choroidal neovascularisation in age-related macular degeneration with verteporfin. Two year results of 2 randomised clinical trials&#;TAP report 2. Arch Ophthalmol ;119:198&#;207.