Age-related macular degeneration (AMD) is a chronic degenerative disease that affects pri- marily the choriocapillaris, Bruch’s membrane, and the RPE. It is the most common cause of legal blindness in the United States and Europe, and the incidence of AMD in Japan has been increasing during the past 20 years. AMD is classified into two types: dry and exudative. The
exudative form, also called disciform macular degeneration, is characterized by the develop- ment of choroidal neovascularization, which causes serous and hemorrhagic detachment of the retina, resulting in poor central vision. The ophthalmoscopic appearance of AMD is shown in Fig. 4.29. Some AMD is treatable with laser photocoagulation, photodynamic therapy, or
4.7 Age-Related Macular Degeneration
Fig. 4.29. Fundus photograph (A), OCT image (B), fluorescein angiogram (C, D each left), and indocyanine green angiogram (C, D each right) of early-phase (C) and late-phase (D) in age-related macular degeneration (AMD) obtained from a 62-year-old man. Present are submacular hemorrhages, a choroidal neovascular membrane, and sensory detachment of the macula. The visual acuity was 0.2
vitreoretinal surgery. Because the condition tends to be self-limiting, retinal function in the periphery is relatively well preserved and com- plete loss of vision is rare.
With both types of AMD, full-field ERGs are usually nearly normal, and the focal macular ERGs and multifocal ERGs demonstrate only abnormal macular function (Fig. 4.30).
Fig. 4.30. Full-field ERGs (A), focal macular ERGs (B), and topographic map of the amplitudes of a multifocal ERG (C) recorded from a patient with AMD
A thick subretinal hemorrhage situated under the fovea occasionally has a natural course that leads to severely decreased visual function even in those without choroidal neovascularization.
Animal experiments have shown that the pho- toreceptors can be damaged by the toxic effects of the iron released by red blood cells as well as by mechanical blockage by the hemorrhage, which hinders metabolic exchange between the photoreceptors and the RPE cells [1].
Subretinal macular hemorrhages can be successfully removed by vitrectomy using tissue plasminogen activator [2], leading to an improvement in the postoperative visual acuity of patients whose vision was good before the hemorrhage [3] (Fig. 4.31).
Changes in the focal macular ERGs elicited by a 10° spot in five patients who had a sub- macular hemorrhage removed by vitrectomy using tissue plasminogen activator are shown in Fig. 4.32. The submacular hemorrhage was caused by rupture of a macroaneurysm in three of the eyes, AMD in one of the eyes, and an unknown reason in the fifth eye. The duration of the subretinal hemorrhage ranged from 3 to 14 days. All of the patients had extremely poor visual acuity (from hand motion to 0.05) before
surgery, and the visual acuity improved to 0.1–0.7 after surgery.
Three points can be made based on these results. First, focal macular ERGs were unde- tectable in all of these patients before surgery regardless of the duration of the submacular hemorrhage. This is definitely different from the results from patients with idiopathic central serous chorioretinopathy, where serous fluid, not blood, accumulates between the photore- ceptors and the RPE. Patients with central serous chorioretinopathy usually have much better visual acuity with good-amplitude focal macular ERGs (see Section 4.1). This difference indicates that blood can alter the function of the photoreceptors much more so than can serous fluid.
Second, the decline of photoreceptor func- tion is partially reversible when blood is removed from the subretinal space even after 14 days, as shown by the recovery of the focal macular ERG in case 5. However, it is more likely that the earlier the blood is removed the better is the recovery. The third point is that there is little if any toxic effect of recombinant tissue plasminogen activator injected at clini- cally useful doses.
4.7.1 How Does Subretinal Hemorrhage
Damage the Retina?
Fig. 4.31. Top: Preoperative fundus photograph with a 10° spot super- imposed on the fovea. The image was obtained while recording the macular ERG in a patient with submacular hemorrhage. Bottom: Postop- erative photograph. The retinal blood is almost completely removed.
(From Terasaki et al. [3], with permission)
Fig. 4.32. Focal macular ERGs recorded from five patients with subretinal macular hemorrhage.
The stimulus spot was 10° in diameter. The fellow eye of case 5 shows no response because of macular degeneration of unknown cause. After surgical drainage of the subretinal hem- orrhage using human plasmino- gen activator, there is partial recovery of the ERG in all patients. (From Terasaki et al. [3], with permission)
Surgical removal of choroidal neovascular (CNV) lesions is undertaken to preserve or regain central neurosensory retinal function as an alternative treatment to conventional laser photocoagulation in eyes with AMD (Fig. 4.33).
The focal macular ERGs elicited by a 15° spot before and after removing CNV lesions in three patients are shown [4] in Fig. 4.34. The ampli- tudes of the a-waves, b-waves, and OPs were markedly reduced or unrecordable with pro- longed implicit times before surgery. These findings indicated severe impairment of macular cone function, which agrees with a his- tological report that there is marked photore- ceptor loss in eyes with AMD. Most patients had
a significant recovery at 3 months after surgery, with the b-wave amplitude selectively increased without an increase in the a-wave amplitude.
These findings suggest further recovery of inner retinal function, particularly the on bipolar cells.
The postoperative increase in b-wave ampli- tude in eyes with preoperative recordable b- waves significantly correlated with the decrease in the mean parafoveal thickness measured by OCT [4] (Fig. 4.35). This suggests that inner retinal function is impaired by retinal edema, and the decreased thickness of the macula con- tributes to the recovery of the inner layer func- tion of the macula.
4.7.2 Removal of Choroidal Neovascular Lesions
Fig. 4.33. OCT images obtained from a 56-year-old man with AMD before and after choroidal neovascular (CNV) lesion removal
Fig. 4.34. Focal macular ERGs recorded from a normal control and three patients with AMD before and after CNV removal. The visual acuity is also shown. (From Terrasaki et al. [4])
Fig. 4.35. Percentage increase in the amplitude of the b-wave and the percentage decrease in the mean parafoveal thickness measured at four points on four sides of the fovea in vertical and horizontal scans. The results are significantly correlated (r= 0.688, P= 0.0076). (From Terasaki et al. [4], with permission)
Although surgical removal of a subfoveal CNV can be performed in some patients with AMD, the main disadvantage of the procedure is reduced visual function that results from damage to the RPE underneath the macula.
Foveal or macular translocation surgery is an operative procedure in which the fovea is moved from diseased RPE onto healthy RPE [5]. This surgery has the potential to improve or preserve central visual function in eyes after removing a subfoveal CNV.
One common technique of macular translo- cation surgery involves a 360° circumferential retinotomy followed by a subretinal infusion of fluid to create total retinal detachment from the RPE. The completely detached retina is then rotated to move the macula from the original position on the RPE to healthy RPE, resulting in a new retina and RPE complex. This compli- cated surgery has been well performed by Terasaki, my colleague, in many patients, and the results have been evaluated [6–8]. The fundus photographs and OCT images of a patient with AMD before and after macular translocation surgery are shown in Fig. 4.36.
From the point of view of retinal physiology, this technique poses several interesting and important issues that should be considered.
First, what is the visual function of the entire retina after it is translocated to the new RPE? To answer this question, full-field ERGs
recorded from three representative patients with AMD before and after macular transloca- tion with 360° retinotomy were compared [6]
(Fig. 4.37). In summary of many patients, the amplitudes of the rod and cone components of the full-field ERGs were reduced by 25%–40%, with slight prolongation of the implicit times after the surgery. Interpreting these results has not been easy because, in addition to translo- cating the entire retina to the new RPE, we had to take into consideration surgical trauma to the retina caused by transient total retinal detachment, the 360° circumferential retino- tomy, and the massive photocoagulation after reattaching the retina. However, the degree of reduction of the full-field ERGs after surgery was surprisingly small, suggesting that the sensory retina can function well at the new RPE site.
Second, how does the shifted macula func- tion on the new RPE? The answer is obtained from the changes in visual acuity and the focal macular ERG before and after surgery [7]. In our large series of patients, visual acuity improved significantly after surgery; moreover, the amplitudes of the focal macular ERGs increased and the implicit times decreased significantly after surgery (Fig. 4.38). These results indicate that the newly located macula does maintain and organize the neural compo- nents well, resulting in improved visual acuity.
4.7.3 Macular Translocation Surgery
Fig. 4.36. Fundus photographs (top) and OCT images (bottom) obtained from a 77-year-old woman with AMD before and after macular translocation with 360° retinotomy. The macula was shifted to the inferior part of the retina, where the RPE underneath the macula was healthy. Her visual acuity improved from 0.06 to 0.60 follow- ing surgery. (From Terasaki et al. [8], with permission)
Fig. 4.37. Full-field ERGs recorded from three representative patients with AMD before and after macular translocation with 360° retino- tomy. (From Terasaki et al. [6])
Fig. 4.38. Focal macular ERGs recorded from three repre- sentative patients with AMD before as well as early (6–12 months) and late (18–30 months) after macular transloca- tion with 360° retinotomy. (From Terasaki et al. [7])
References
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