Ординатура / Офтальмология / Английские материалы / Textbook of Vitreoretinal Diseases and Surgery_Natarajan, Hussain_2008
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Textbook of Vitreoretinal Diseases and Surgery
studies. The three line gainers were 35% but the number of injections could be reduced to 9.9 injections in 2 years.
Variable Dosing of anti-VEGF Drugs using OCT
Presently, the most important use of OCT in AMD is to guide the treatment with anti-VEGF drugs. Fung et al10 reported the use of OCT in the treatment of AMD. A drop in visual acuity by 5 letters, an increase in macular thickness by 100 microns or presence of new fluid were indications for retreatment. Using these parameters,the number of injections were 5.5 in one year. This appeared to be a practical guideline. Hence, increase in thickness by 100 microns, presence of new fluid or persistence of fluid—intraretinal, subretinal or sub-RPE would necessitate re-injection of anti-VEGF drugs. A patient with Occult CNVM was injected with the loading dose of 3 injections of Ranibizumab. Re-injections were based on OCT findings (Figures 13-12 to 13-14). There was recurrence of subretinal fluid and sub RPE fluid at 6 months and hence was re-injected with ranibizumab.
Using a combination of assessments which include OCT (both quantitative and qualitative) and vision, would prevent inadequate treatment. Figures 13-15 to 13-19 shows a patient with significant subretinal hemorrhage secondary to AMD. He underwent pneumatic displacement following which observed to have a CNVM. He underwent intravitreal injections with ranibizumab. The quantitative analysis showed normal central macular thickness however on qualitative assessment there was persistence of sub retinal fluid for which he was re-injected with ranibizumab. On follow-up, subretinal fluid was absent and he was advised follow-up.
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FIGURE 13-12: Pre-treatment fundus picture, FFA and OCT of an occult CNVM
Optical Coherence Tomography in Age-related Macular Degeneration
FIGURE 13-13: Post-treatment fundus photo, FFA and OCT at 3 months showing regression of CNVM
FIGURE 13-14: Fundus photo and OCT of the same
patient at 6 months showing recurrence of subretinal 159 fluid and sub-RPE fluid
Textbook of Vitreoretinal Diseases and Surgery
FIGURE 13-15: OCT image of submacular hemorrhage due to AMD
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FIGURE 13-16: Quantitative OCT( Retinal thickness map) prior to treatment with |
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ranibizumab showing increased central macular thickness |
Optical Coherence Tomography in Age-related Macular Degeneration
FIGURE 13-17: Quantitative OCT( Retinal thickness map) post-treatment follwing loading dose of ranibizumab showing normal central macular thickness
FIGURE 13-18: OCT image showing persistence of subretinal fluid even after injection of ranibizumab
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FIGURE 13-19: OCT image showing normal macular contour and resolution of subretinal fluid after retreatment
FIGURE 13-20: Showing the biphasic response of AMD to ranibizumab.(Courtesy: Novartis Ophthalmics, India. Lucentis product monograph first edition 2007, Novartis, Basel Switzerland)
Figure 13-20 demonstrates the present role of OCT in the maintenance phase when anti-VEGF drugs are used in the management of AMD. The goal is to sustain the visual gain with the least number of injections.
Future
The use of ultra-high resolution OCT in dry AMD had showed its ability to detect early neovascular changes not visible clinically or by angiography.22 The ultra-high resolution OCT defines the outer retinal layers better.
Spectral domain OCT would play a major role in the management of AMD as it has the ability to provide different layers for analysis and provide a 3-D rendering of the image (Figure 13.21). It has higher resolution and faster acquisition time. The higher resolution is due to the increased bandwidth of the existing laser (50 nm) as well as Fourier domain transformation eliminating the mechanical
162 mirror. This allows 20,000-30,000 A scans per minute compared to 400 A scans in Time domain OCT.22
Optical Coherence Tomography in Age-related Macular Degeneration
FIGURE 13-21: Spectral OCT showing the 3-D rendering of the retinal image
References
1.Gupta V, Gupta A, Dogra MR. Atlas optical coherence tomography. Jaypee Brothers Medical Publishers, 2004.
2.Talks J, Koshy Z, Chatzinikolas K. Use of OCT, fluorescein angiography and ICG angiography in screening clinic for wet AMD. Br J Ophthalmol 2007; 91(5): 600-1.
3.Goff MJ, Johnson RN, McDonald HR, Ai E, Jumper JM, Fu A. Intravitreal Bevacizumab in previously treated choroidal neovascularisation in AMD. Retina 2007;27(4):432-8.
4.Eter N, Bindewald A, Roth F, Holz FG. OCT in AMD: findings, usage in clinical routine and treatment outcome, Ophthalmologe 2004;101(8): 794-803.
5.Brancato R, Introini U, Pierro L, Setaccioli M, Forti M, Bolognesi G, Tremolada G. OCT in retinal angiomatous proliferans. Eur J Ophthalmol 2002;12(6): 467-72.
6.van Velthoven ME, de Smet MD, Schlingemann RO, Magnani M, Verbraak FD. Added value of OCT in evaluating the presence of leakage in patients with age-related macular degeneration treated with PDT.
7.Ozdemir H, Karacorlu SA, Karacorlu M-Early optical coherence tomography changes after photodynamic therapy in patients with age-related macular degeneration. Am J Ophthalmol 2006;141(3): 574-6.
8.Sahni J, Stanga P, Wong D, Harding S. Optical coherence tomography in photodynamic therapy for subfoveal choroidal neovascularisation secondary to age-related macular degeneration, a cross sectional study. Br J Ophthalmol 2005;89(3): 316-20.
9.Emerson MV, Lauer AK, Flaxel CJ, Wilson DJ, Francis PJ, Stout JT, Emerson GG. Intravitreal Bevacizumab (Avastin) for neovascular age-related macular degeneration. Retina 2007;27(4): 439-44.
10.Fung AE, Lalwani GA, Rosenfeld PJ, Dubovy SR, Michels S, Feuer WJ, Puliafito CA, Davis JL, Flynn HW, Esquiabro M. An OCT guided variable dosing regimen with intravitreal Ranibizumab for neovascular AMD. Am J Ophthalmol 2007;143(4): 566-83.
11.Rosenfeld P. Two-year results of an optical coherence tomography-guided variable-dosing regimen with ranibizumab (Lucentis[R]) in neovascular AMD: the PrONTO study. Program and abstracts of the 40th Annual
Scientific Meeting of the Retina Society, September 27-30, 2007, Boston, Massachusetts.
12. Politoa A, Napolitano MC, Bandello F, Chiodini RG. Role of OCT diagnosis of RAP in patients with AMD. Ann 163 Acad Med Singapore 2006; 35(6): 420-4.
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13.Augustin AJ, Puls S, Offermann I. Triple therapy for choroidal neovascularization due to age-related macular degeneration. Retina 2007; 27(2): 133-140.
14.Ferrara N, Diamico L, Shams N et al. Development of Ranibizumab, an anti-vascular endothelial growth factor antigen binding fragment, as therapy for neovascular age-related macular degeneration. Retina 2006; 26(8): 85970.
15.Spitzer MS, Wallenfels-Thilo B, Sierra A, Yoeruek E, Peters S, Henke-Fahle S, Bartz-Schmidt KU, Szurman P, Anti proliferative and cytotoxic properties of Bevacizumab on different ocular cells. Br J Ophthalmol 2006;90(10): 131621.
16.Rosenfeld PJ, Brown DM, Heier JS Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 2006;355: 1419-31.
17.Brown DM, Kaiser PK, Michels M –Ranibizumab versus vertiporphin for neovascular age-related macular degeneration. N Engl J Med 2006;355:1432-44.
18.Brown DM Lucentis. PIER data Retinal Physician 2006 symposium, May31June3 2006, Atlantis, Bahamas.
19.Leung CK, Chan WM, Chong KK, Chan KC, Yung WH, Tsang MK, Tse RK, Lam DS. Alignment artifacts in optical coherence tomography analyzed image. Ophthalmology 2007;114(2): 263-70.
20.Ray R, Stinnett SS, Jaffe GJ. Evaluation of image artifact produced by optical coherence tomography of retinal pathology. Am J Ophthalmol 2005;139(1):18-29.
21.Debating the treatment of ARMD, conference coverage, Medscape ophthalmology, Dec 2007. www.medscape.com.
22.Pieroni CG, Witkin AJ, Ko TH, Fujimoto JG, Chan A, Schuman JS, Ishikawa H, Reichel E, Duker JS. Ultrahigh resolution OCT in non exudative age related macular degeneration. Br J Ophthalmol 2006;90(2):191-7.
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Introduction
The retinal burn was first produced by Meyer-Schwickerath using sunlight in 1960.1 This was followed by the introduction of Xenon-arc photo coagulators. However due to intense retinal burns of large size, these were replaced by the laser based systems in the 1970s. Over the next 30 years, few changes were seen in the laser systems. Some of the notable changes were the change from gas based lasers to solid state lasers with the advantage of portability and lower maintenance. The most commonly used lasers are the Frequency doubled Nd-YAG laser (532 nm) and the infrared diode laser (810 nm). There has been a constant endeavor for better technology to overcome the problems of the presently available lasers.
Photocoagulation—Conventional Laser
Though the effect of the laser is on the RPE there is concurrent damage to the choriocapillaris and the neural retina. There is an increase in the size of the burn over time. Maeshima 2 reported an annual increase of size of the laser burn by 12.5% and this was observed to be more in the posterior pole and with the use of longer wavelength lasers (Figure 14-1). The retinal laser burn is surrounded by an area of latent thermal damage which manifests over time. Some of the reported side effects are loss of visual field, contrast sensitivity and night blindness.3-5 Some of the research has been focused on the use of lasers which has minimal side effects while maximizing therapeutic effect.
The options are (1) Change in the method of treatment: Light photocoagulation and Minimum intensity photocoagulation (MIP) or Micropulse laser and (2) Change in instrumentation: PASCAL laser.
CHANGE IN THE METHOD OF TREATMENT
Light Photocoagulation
Studies4,6 have shown that when the power is adjusted to produce a barely visible burn, the effects on the retina appear to be similar to standard burns. Bandello et al4,6 reported no difference in the visual outcome or reduction in high risk proliferative diabetic retinopathy characteristics in pan retinal photocoagulation from either the light burns or classic burns. Similar findings were observed in macular focal or grid laser. The reduction in macular edema and improvement in vision were similar in both the groups.6 The complication rate was reported to be less.4 Larger multicentre trials would provide us an answer whether reducing the iatrogenic damage to the retina can achieve beneficial effect on the disease control.
Minimum Intensity Photocoagulation
Dorin 7 suggested that the standard photocoagulation is a photo-thermal reaction and effects results in release of more biologic agents from an area adjacent to the burnt tissue. This area is partially affected and hence is biologically active. The area of burn ends up as an atrophic scar and is an inactive area (Figures 14-1 and 14-2). So, the purpose of iatrogenic damage caused by present techniques appears inappropriate. Hence, use of non lethal thermal burns without visible end point during the treatment would be desired. This happens to be the principle behind Minimum Intensity
166 photocoagulation theoretically sparing the retina and thus incurring minimal side effects.7
Newer Advances in Retinal Lasers
FIGURE 14-1: Argon laser done 9 years back. The scars show significant enlargement and tend to become confluent
Micropulse Laser
The effect on the Retinal pigment epithelium (RPE) appears to be the most important laser-tissue reaction.5,7 It has been postulated that the effect on RPE would improve oxygen diffusion from the choriocapillaris to the inner retina, release of factors which inhibit neovascularization and improve absorption of edema at the macula.
As the name suggests, micropulse laser has duration in microseconds compared to milliseconds in conventional laser. Since one laser spot cannot produce a biological effect, a train of pulses is used. The laser used is 810 nm laser and in pulse duration of 2000 microseconds (2 milliseconds) the laser is on for 100 to 300 microseconds and the frequency is about 400-500 pulses per second. As shown in
Figures 14-3 and 14-4 as the energy per spot get reduced the effect gets more and more confined 167 and in micropulse laser is confined to the RPE.5,8