In nonproliferative diabetic retinopathy, vision may be impaired by macular edema and exudates resulting from breakdown of the inner blood–retinal barriers at the level of the retinal capillary endothelium. Many patients with long-term diabetes mellitus will gradually develop diffuse obliteration of the retinal microcirculation, especially of the capillaries, resulting in generalized retinal ischemia. This ischemic state leads to neovascularization of the retina and iris, at least partly mediated by diffusible vasoproliferative factors released from the ischemic retina into the ocular fluids. Untreated retinal neovascularization leads to vitreous hemorrhages and traction retinal detachment. Iris neovascularization leading to neovascular glaucoma is rare unless the patient has had vitreoretinal surgery. (The clinical features of diabetic retinopathy are more fully discussed in Chapter 10.)
Diabetic macular edema can be treated by focal or grid pattern laser photocoagulation, which principally acts by augmenting the function of the retinal pigment epithelium, rather than by direct closure of microaneurysms as previously suggested. Burns 50–100 μm in diameter are applied, avoiding the foveal avascular zone, which is approximately 500 μm in diameter. The areas of leakage to be treated can be identified by clinical examination (zones of retinal thickening), by fluorescein angiography (areas of discrete or diffuse fluorescein leakage and areas of capillary nonperfusion associated with retinal thickening), or now usually by optical coherence tomography (OCT). Burn intensity (laser power setting) depends on the laser used. Using a shorter-wavelength laser (green or yellow), a slight change in color is required. Using a longer-wavelength laser (diode), the burn should be almost invisible. Diode micropulse and argon green lasers are equally effective at reducing the edema, but laser scars are 8 times more likely to be visible after argon green laser and there is tendency to better visual outcome with diode micropulse laser, with which theoretically there is reduced likelihood of progressive expansion of the area of laser damage.
The most effective treatment for retinal and iris neovascularization is PRP, which usually consists of treating the entire retina except for the area within the temporal vascular arcades, with burns 200–500 μm in diameter separated by 0.5–1 burn diameter (Figure 23–1). PRP requires a total of at least 2000 and sometimes 6000 or more burns, usually delivered over two or more sessions spaced 1–2 weeks apart. Retrobulbar, peribulbar, or sub-Tenon anesthesia is sometimes required, particularly if areas of the retina need to be treated again because of recalcitrant or recurrent neovascularization. Treatment is staged to reduce the incidence of uveitis, macular edema, exudative retinal detachment, and even shallowing of the anterior chamber with secondary angle closure. If there is significant macular edema, usually focal macular photocoagulation is performed before or together with PRP to avoid increase in edema. Intravitreal or orbital floor steroid (Triamcinolone) injection may prevent rebound macular edema after PRP. Currently it is restricted to patients requiring PRP and macular laser at the same time.
Adequate PRP is highly effective in producing regression of neovascularization. The exact mechanism of action has not been established, but reduction in the degree of retinal ischemia and production of diffusible vasostimulative substances are thought to be important. Reduction of ocular blood, suggesting reduction of oxygen demand in the retina, has been demonstrated after PRP. The type of laser used does not appear to influence the efficacy of PRP, but particular characteristics can be important in treatment, for example, the easier use of the diode infrared laser in the presence of vitreous hemorrhage and the more rapid laser delivery of the PASCAL.
PRP does not cause regression of the fibrosis associated with retinal neovascularization, which is responsible for tractional retinal detachment. Furthermore, PRP can be precluded by vitreous hemorrhage. Thus, PRP should be undertaken as soon as high-risk characteristics have developed. These include any new vessels on the disk with vitreous or preretinal hemorrhages, significant new vessels on the disk, and significant new vessels elsewhere with vitreous or preretinal hemorrhages.
Laser and other therapies are so effective in preventing blindness in diabetes that screening of asymptomatic diabetics for retinopathy is very worthwhile.
Central Retinal Vein Occlusion
Central retinal vein occlusion produces the classic fundus appearance of disk swelling, marked venous dilation, and almost confluent retinal hemorrhages (see Chapter 10). While these changes can progress to retinal neovascularization, vitreous hemorrhage, and fibrosis, a more common complication is the development of rubeosis iridis with neovascular glaucoma. If severe retinal ischemia is present on fluorescein angiography, there is a 60% chance of this complication. In neovascular glaucoma, substances produced by the ischemic retina diffuse forward and stimulate formation of a fibrovascular membrane that grows across the iris surface and covers the trabecular meshwork, resulting in glaucoma characterized by very high pressure, pain, and marked resistance to medical and surgical therapy, so that enucleation of the blind and painful eye may be required. PRP as described above for treatment of proliferative diabetic retinopathy—preferably with the krypton red or diode infrared laser to avoid preretinal fibrosis caused by heat absorption in the hemorrhages—can greatly reduce the incidence of neovascular glaucoma in ischemic central retinal vein occlusion. It is most effectively applied when iris neovascularization is present but before neovascular glaucoma has developed. However, in clinical practice, this timing can be difficult to achieve. Once neovascular glaucoma is present, adequate panretinal photocoagulation, possibly preceded by intra-vitreal injection of an anti-VEGF (Vascular Endothelial Growth Factor) agent, will usually cause regression of the anterior segment neovascularization, allowing the glaucoma to be controlled medically or by filtering surgery. Unfortunately, established neovascular glaucoma is often associated with corneal edema, miosis, or hyphema, so that PRP cannot be performed and only cyclophotocoagulation or enucleation can be used. For this reason, prophylactic PRP may be advisable in all cases of ischemic central retinal vein occlusion. A relative afferent pupillary defect, vision worse than 20/200, and multiple retinal cotton-wool spots are highly suggestive of ischemia severe enough to warrant prophylactic PRP. Electroretinography and fluorescein angiography provide further evidence when needed.
Laser treatment is ineffective for macular edema due to central retinal vein occlusion.
Branch Retinal Vein Occlusion
This condition varies from localized areas of venous congestion and hemorrhage to hemiretinal involvement from occlusion of the superior or inferior division of the central retinal vein (see Chapter 10). The principal complications are chronic macular edema (with or without exudates) and retinal neovascularization followed by vitreous hemorrhage. As the risk of neovascular glaucoma is extremely low, there is no evidence that prophylactic PRP is justified; however, if retinal neovascularization does develop, laser treatment should be performed promptly, preferably before vitreous hemorrhage occurs.
Focal and grid-pattern argon green laser photocoagulation, by obliterating areas of retinal leakage demonstrated by fluorescein angiography, is used to treat macular edema when vision is 20/40 or worse and 3 months have elapsed since the venous occlusion.
When a peripheral retinal tear occurs—usually due to posterior vitreous detachment causing vitreous traction—the patient often notices the sudden appearance of dot-like floaters. The tear can lead to retinal detachment, but if it is detected prior to the accumulation of subretinal fluid, it can be walled off by applying a double ring of laser burns around it to create an adhesion of the adjacent attached retina to the pigment epithelium. With modern contact lens, such as the Superquad 160, this can be achieved in most cases with a slitlamp laser delivery system. In the remaining few, indirect laser should be considered. Once retinal detachment has occurred, surgery is required. Prompt retinal examination through a dilated pupil is therefore indicated in any eye with sudden onset of floaters—particularly dot-like floaters suggesting red blood cells.
Macular Degeneration & Related Diseases
Bruch's membrane forms a barrier layer between the retinal pigment epithelium and the choriocapillaris, which is the capillary layer of the choroid. If Bruch's membrane deteriorates or is damaged, choroidal neovascularization can grow through the break beneath the pigment epithelium, first causing exudative pigment epithelial detachment with distortion and edema of the overlying retina and later causing hemorrhage and fibrosis with destruction of retinal function in that area. The macula is particularly likely to develop Bruch membrane breaks and choroidal neovascularization, although these changes can occur anywhere in the fundus. The most frequent cause is age-related macular degeneration, which presents initially as asymptomatic yellowish deposits (drusen) in the macula. As the years advance, pigment epithelial atrophy and clumping are seen; finally, Bruch membrane breaks appear, leading to choroidal neovascularization, fibrosis, and loss of central vision. This condition is the leading cause of legal blindness in the developed world. Bruch membrane breaks and choroidal neovascularization can occur at sites of old chorioretinitis from childhood histoplasmosis, toxoplasmosis, and various other inflammatory disorders. They can develop from traumatic choroidal ruptures—even in children—and can occur in a host of hereditary diseases involving the retina.
Anti-VEGF therapy by repeated intra-vitreal injections has become the preferred treatment for choroidal neovascularization associated with age-related macular degeneration (neovascular AMD), particularly subfoveal disease (see Chapter 10). If choroidal neovascularization is located away from the central foveal area (extrafoveal), it can be destroyed by careful laser photocoagulation to preserve central vision. The yellow macular pigment (xanthophyll) strongly absorbs blue light, weakly absorbs green light, and does not absorb yellow, orange, or red light (Table 23–1). Hemoglobin strongly absorbs blue, green, yellow, and orange light but very weakly absorbs red light. Melanin absorbs all visible wavelengths. Selective absorption of laser energy is therefore possible. If the neovascular net has melanin pigment in it or is bleeding, then krypton red laser light allows deep penetration to the choriocapillaris without hemoglobin or xanthophyll absorption. If the net does not have much melanin and has not bled, argon green or dye laser yellow or orange will be absorbed by hemoglobin to coagulate the net but the scattered light will not be absorbed by xanthophyll. The whole area of choroidal neovascularization must be heavily treated (Figure 23–2).
Choroidal neovascularization. Fundus fluorescein angiogram in early venous (A) and late phase (B). C: Fundus color photograph immediately after laser therapy. Fundus color photograph (D) and fundus fluorescein angiogram (E) 6 months after laser therapy showing retinal scarring.
Photodynamic therapy (PDT), in which an intravenous injection of a photosensitive dye (verteporfin), believed to localize within the choroidal neovascularization, is followed by treatment with a laser optimized for activation of the dye to cause thrombosis of the abnormal blood vessels, previously was the preferred treatment for subfoveal predominantly classic choroidal neovascularization associated with AMD With the development of anti-VEGF therapy, the role of PDT had greatly reduced in the management of choroidal neovascularization but remains useful under certain circumstances for other conditions.
Treatment of open-angle glaucoma, angle-closure glaucoma, and glaucoma resistant to surgery has been radically altered by availability of effective laser techniques.
In primary angle-closure glaucoma, aqueous flow through the pupil is blocked by contact of the lens with the posterior surface of the iris. The resulting pressure in the posterior chamber forces the peripheral iris forward into contact with the trabecular meshwork, blocking outflow and increasing intraocular pressure. While the classic dramatic acute glaucoma attack is usually considered the prototype of angle-closure glaucoma, acute attacks are actually very rare. Creeping or subacute angle-closure glaucoma is far more common, especially in darkly pigmented eyes, and can occur with a normal central anterior chamber depth. Angle closure can be determined only by examining the anterior chamber angle by gonioscopy (see Chapters 2 and 11). Because angle closure is the most common type of glaucoma in Asian populations, it is probably the most common type of glaucoma worldwide. Surgical iridectomy was the standard treatment for angle-closure glaucoma for decades but carried the risks of hemorrhage, infection, anesthetic accidents, and even sympathetic ophthalmia.
Laser iridotomy was made more effective by the Abraham contact lens (with a 66-diopter focusing button) and the Wise iridotomy-sphincterotomy lens (103-diopter button) that increase energy density and improve visualization of the iris. With these high-energy densities, laser iridotomy (Figure 23–3) is often successful with either the argon laser or the Q-switched Nd:YAG laser, failing only when the cornea is so cloudy that the laser cannot be focused upon the iris. Alternative laser therapy may then be required (see later in the chapter).
Laser iridotomy for angle-closure glaucoma.
With the argon laser, the beam is focused through the iridotomy lens upon the far peripheral iris fibers, which are cut in a line parallel to the limbus by multiple shots at 0.01 or 0.02 seconds exposures and high-energy levels. With the Nd:YAG laser, iridotomy can be done through the iridotomy lens by a high-power single-point method using about 5–10 mJ per shot in a single-shot burst. The iridotomy can be enlarged by cutting the far peripheral iris fibers in a line parallel to the limbus with multiple shots at 1–2 mJ. The argon laser is preferable for dark brown, thick irides, which tend to bleed with the Nd:YAG laser, while light blue irides do not absorb argon laser energy well and are more easily perforated with the Nd:YAG laser. If both lasers are available, a very efficient method for thick brown irides is to cut the thick stroma with the argon laser and then remove strands and pigment with a few low-power Nd:YAG laser bursts. Because of its safety, laser iridotomy should be done not only for established angle-closure glaucoma but whenever progressive pupillary block is occurring, before irreversible damage from angle closure has occurred.
When the cornea is too cloudy to permit laser iridotomy for acute angle-closure glaucoma, argon laser peripheral iridoplasty can be attempted. To contract the iris stroma near the angle, a ring of contraction burns—low power (about 200 mW), long duration (0.5 seconds), and large spot size (500 μm)—is placed on the peripheral iris using the standard iridotomy lens. This mechanically pulls open the angle, thus lowering the intraocular pressure and allowing iridotomy to be performed. It has been shown to be as effective as medical therapy but sometimes causes discomfort. A combination of both laser and medical therapies is usually employed.
This is the most common type of glaucoma in Western countries and is characterized by painless gradual reduction in trabecular meshwork function with decreasing outflow, increasing intraocular pressure, progressive cupping of the optic nerve, and insidious loss of visual field, leading ultimately to blindness.
Topical medical therapy is the standard initial approach. If medical therapy is inadequate or unacceptable to the patient, argon or frequency-doubled Nd:YAG laser trabeculoplasty may be indicated (Figure 23–4). This consists of spacing 100 or more nonperforating laser burns 360° around the trabecular meshwork to shrink the collagen in the tissues of the trabecular ring, reducing the circumference, and therefore the diameter of the trabecular ring, thus pulling the trabecular layers apart with reopening of the intertrabecular spaces and of Schlemm's canal. Growth of new trabecular cells may also occur. Trabeculoplasty increases outflow and has no influence upon aqueous secretion.
Argon laser trabeculoplasty burns in the trabecular meshwork. A: Visualized by gonioscopy. B: Diagram.
The value of trabeculoplasty lies in reducing or avoiding medical therapy and postponing or avoiding the risks of drainage surgery. It seems to be most effective in patients with pseudoexfoliation and pigmentary glaucoma. In most other patients, the effect is relatively short-lived (1 or 2 years), but it may be preferable to trabeculectomy in black patients with advanced glaucoma. The main side effects are a rise in pressure for 1–4 hours in about one-third of eyes, usually preventable by pretreatment with apraclonidine drops, and a rise in pressure for 1–3 weeks in about 2% of treated eyes. Initial treatment with 50 laser burns in 180° of the trabecular meshwork, followed by treatment to the other 180° at a later date if necessary, reduces the severity of these pressure rises. Subsequent loss of pressure control can be very sudden after trabeculoplasty, and thus requires more frequent follow-up than in patients stabilized on medical therapy.
Selective laser trabeculoplasty (SLT) delivers very high energy of extremely short duration, with minimal damage to the trabecular meshwork on histopathological studies. It is as effective as conventional trabeculoplasty but is easier to perform as the laser spot is larger and only needs to be aimed at the whole trabecular meshwork, and can be repeated.
Glaucoma refractory to the usual operative procedures can often be controlled by direct destruction of the ciliary processes. This was first done by diathermy and later by cryosurgery. Cyclophotocoagulation through intact conjunctiva and sclera was originated by Beckman, using a high-energy ruby laser, but is currently performed by contact delivery through a fiberoptic probe with thermal-mode Nd:YAG laser or diode laser (Figure 23–5). Good control is usually obtained, but multiple treatments may be required. Side effects such as pain, inflammation, and reduction of vision are significantly less severe than with cryosurgery. Laser endocyclophotocoagulation can be performed using a fiberoptic probe passed through the pars plana during vitrectomy.
Laser cyclophotocoagulation. The laser light passes through the conjunctiva and sclera and is absorbed by the pigment in the ciliary body, producing thermal coagulation of secreting epithelium.
Trabeculectomy remains a popular method of glaucoma drainage surgery (see Chapter 11). In order to increase the degree of drainage and perhaps achieve greater long-term reduction in intraocular pressure—similar to that obtained with the older full-thickness drainage procedures—laser lysis of the partial-thickness scleral flap sutures can be performed in the early postoperative period. The black 10–0 nylon sutures are cut by focusing short-laser pulses upon them through the transparent conjunctiva, aided by compressing the overlying tissues with the Hoskins suture lens. The argon laser may be used, but if hemorrhage is present the krypton red or diode infrared laser is preferred to avoid flap perforation by hemoglobin absorption of argon blue-green laser wavelengths.
Posterior & Anterior Capsulotomy after Cataract Surgery
Modern cataract surgery uses phacoemulsification followed by posterior chamber intraocular lens implantation (see Chapter 8). If the posterior capsule supporting the intraocular lens later opacifies, vision can be restored by focusing Q-switched Nd:YAG laser pulses just posterior to the capsule to produce a central capsulotomy (thus avoiding further intraocular surgery). Careful focus through a condensing contact lens is necessary to avoid damage to the intraocular lens. There is a small increase in the risk of retinal holes and retinal detachment after capsulotomy, especially in high myopes. Opacification of the capsule is not preventable at present, although modern intraocular implants have a significantly lower rate.
Anterior capsular fibrosis may lead to contracture and occlusion of the visual axis. Radial incisions with the Q-switched Nd:YAG may obviate intraocular surgery.
Incomplete clearance of vitreous from the anterior chamber during the management of vitreous loss secondary to trauma or surgery may result in pupillary distortion, chronic uveitis, and cystoid macular edema. The vitreous bands can be cut with the Q-switched Nd:YAG laser, using a condensing corneal contact lens. Topical pilocarpine constricts the pupil, thus tightening the vitreous strands to allow easier cutting. Multiple shots at minimal optical breakdown levels should be used to minimize concussion to cornea and iris. Although eyes with chronic cystoid macular edema have improved after cutting of vitreo-corneal bands, the bands should be cut as soon as they have been identified and before the development of these complications.
Vaporization of Lid Tumors
The carbon dioxide laser has been used to bloodlessly remove both benign and malignant lid tumors. However, because of scarring, lack of a histologic specimen, and inability to assess margins, laser treatment for this purpose appears inferior to surgery in most cases of malignant tumors.
Corneal Refractive Surgery
The excimer lasers, particularly the 193-nm wavelength argon fluoride laser, can evaporate tissue very cleanly with almost no damage to cells adjacent to or under the cut. By using multiple pulses and progressively changing spot size to evaporate successive thin layers of the cornea, computer-controlled recontouring of the cornea (photorefractive keratectomy [PRK]) can precisely correct moderate myopic and astigmatic refractive errors (Figure 23–6). Hyperopic and highly myopic (over 6 diopters) errors respond less well. Although it quickly replaced radial keratotomy, in which radial incisions are made in the cornea with a blade and is less predictable, as well as being associated with complications—for example, deep scarring, ocular perforation, intraocular infection, and late hyperopic shift—PRK removes Bowman's membrane to which the corneal epithelium adheres, which can sometimes produce corneal haze. LASIK, in which a hinged lamellar flap of cornea is cut with a mechanical keratome, or with the femtosecond laser (IntraLASIK), the necessary laser ablation of the corneal bed is performed, and the flap replaced (Figure 23–7), preserves Bowman's membrane, and also provides faster visual recovery and less discomfort but with a slightly higher risk of long-term complications, especially in thin corneas. LASEK and epithelial LASIK (epi-LASIK), in which the flap is limited to the epithelium, potentially combine the benefits of both PRK and LASIK.
Excimer laser photorefractive keratectomy. The laser cleanly photodecomposes corneal tissue in a controlled pattern to reshape the corneal curvature. (Photo courtesy of T Clapham, VISX Inc.)
LASIK. Diagrams of corneal flap (A) and multiple laser spots (B).
Modern excimer lasers have a smaller spot size, an eye-tracking system, and wavefront custom ablation. These improve accuracy of treatment and reduce the increase of spherical aberration induced by the corneal flap. Wavefront custom ablation is believed to cause fewer postoperative night-vision problems.
Excimer lasers can also be used therapeutically (phototherapeutic keratectomy—PTK) to remove superficial corneal opacities such as those associated with band keratopathy and to treat superficial corneal disease such as recurrent corneal erosions.
Cosmetic Laser Eyelid Surgery
Exposing wrinkled eyelid skin to repeated 1-ms pulses from the carbon dioxide laser—obtained by rapid pulsing of the laser tube or by computer-controlled rapid scanning of a continuous small laser beam—evaporates the epidermis and induces collagen contraction in the dermis. When the epithelium regenerates, the skin is tightened and small wrinkles and crow's feet are removed. The technique is more precise than older methods such as dermabrasion or chemical peels, but it still can sometimes be complicated by keloid scarring, hyperpigmentation, and herpesvirus infection. Surgeon experience is very important in obtaining good results. The erbium:YAG laser can be used in the same manner.
Green laser can also be used to remove xanthalesma. It is very effective but can cause depigmentation and should be avoided in darkly pigmented skin.
Confocal imaging is a video method that uses a rapidly scanning tiny laser spot whose reflected light is imaged through a pinhole upon a detector, thus suppressing all reflections except those from the focal plane. By scanning at multiple levels and then combining the images by computer processing, precise and reproducible 3-dimensional images of ocular structures can be produced. The principal use of these instruments is to evaluate and follow glaucoma-induced changes in the optic nerve head, but other uses include macular, lens, and corneal imaging. Laser interferometry is used to measure blood flow in the ciliary body and retinal blood vessels. Optical coherence tomography (OCT) can produce very high-resolution optical sections of the cornea, anterior segment, and retina to allow evaluation of diseases such as angle-closure glaucoma and macular edema.