Ординатура / Офтальмология / Английские материалы / Age-Related Changes of the Human Eye_Cavallotti, Cerulli_2008

Further anterior-posterior and dynamic vitreous traction progresses from foveal detachment to macular hole formation. Gass historic theory could be partially confirmed with optical coherence tomography (OCT) findings.3 However, macular hole formation and spontaneous macular hole closure were documented in eyes with and without complete PVD.4 The etiology of macular holes seems to be multifactorial, including vitreomacular traction, foveolar dehiscence, and other factors. Trauma and high myopia are the causative factors most frequently seen.5

Most patients presenting FTMHs are older than 55 years, and female patients are predominately affected (male: female = 1: 2-3). The overall prevalence is approximately 3.3 cases in 1000 in this age group.6 The risk for development of an idiopathic FTMH in the fellow eye is approximately 6.5 percent within five years.

In Gass classification of the development of macular holes, Stage 1 is foveal detachment characterized by loss of foveal depression and the appearance of a yellow spot (stage 1A, 50-100 m) or a yellow ring (stage 1B) due to the distribution of xanthophylls. Stage 2 results in early hole formation with a full-thickness macular opening. Vitreous separation in the macular area then leads to Stage 3. Complete and obvious posterior vitreous separation, along with a full-thickness macular hole, constitutes Stage 4.7

Diagnostic Tools

In most cases, careful biomicroscopy slit-lamp examination with a contact lens allows to us diagnose a FTMH. Clinically, an early stage idiopathic macular hole is often undetectable. With progression, a round excavation with punched-out borders interrupting the slit-lamp beam can be seen. A grayish halo corresponding to serous detachment surrounds an often red area with a yellow spot or ring corresponding to accumulation of xanthophylls. An operculum may be seen as sign of vitreous separation.

During the examination, the patient notices a discontinuity in the slit-lamp beam as it passes over the hole (positive Watzke-Allen test). Some false-positive results, however, are possible.

Alternatively, a 50 mm spot laser-aiming beam, shown directly in the center of the macular, will not be seen in patients with macular holes (positive laser-aiming beam test). Fluorescein angiography (FAG) is rarely necessary in patients with FTMH. The angiographic findings present a hyperfluorescence in the macular area. Other techniques, such as the scanning laser ophthalmoscope (SLO) and fundus autofluorescence have also been used to evaluate the extent of the lesion. The SLO has shown that the visual loss in eyes with macular holes is related to the absence or reduction of function in the area of the neurosensory defect.8 Autofluorescence imaging demonstrates a marked hyperfluorescent spot in the foveolar region, which disappears after successful surgical treatment.9

During the last few years, the OCT has become the gold standard for the diagnosis of FTMHs. On OCT images, a Stage 1 macular hole appears as a distinct foveal thickening often with a large intraretinal cyst present under the fovea (Stage 1A between 100200 m; Stage 1B between 200-300 m). Linear reflections corresponding to the

posterior vitreous face are typically noted inserting at the central fovea. Stages 2 through 4 represent an enlarging full thickness defect through the neurosensory retina (Stage 2 less than 400 m; Stage 3 and 4 more than 400 m) and an increasing anterior-posterior vitreous traction resulting in separation of the vitreous body from the surface of the retina (Stage 3 no signs of PVD, often pseudo-operculum; Stage 4 complete PVD). The advantage of the OCT over biomicroscop

g of retinal layers, new technologies with increased

resolution have been introduced. The ultrahigh resolution OCT (UHR-OCT) provides improved imaging of epiretinal, intraretinal, and subretinal layers. The UHR-OCT is useful in distinguishing between FTMH and MPH or LMH, and enables the visualization of changes in the photoreceptor morphology. MPHs have a nearly normal, or slightly increased, central foveal thickness and a steepened foveal pit with thickened retinal edges. In contrast, LMHs have a thinner central foveal thickness, and an irregular foveal center with split edges.1 The visualization of the junction between the photoreceptor’s inner and outer segments was found to be an important indicator of photoreceptor integrity. Consequently, their integrity or impairment seems to be an indicator of macular hole progression and surgical outcome.10 Three-dimensional UHR-OCT imaging enables new imaging protocols—comparable with optical biopsy—that improve visualization and mapping of retinal microstructure11 (see Figs. 13.1a, 13.1b, and 13.1c).

Most patients with FTMHs notice a gradual decrease in visual acuity (VA), blurred vision, and/or metamorphopsia in the affected eye. Rarely, they complain of a central scotoma. Vitreomacular traction ma y result in photopsia and the sudden onset of floaters. The VA of patients varies according to size, location, and the stage of the FTMH. Patients with Stage 1 FTMHs usually retain a good VA, ranging between 1.0 and 0.33. Once a macular hole represents a full-thickness defect through the neurosensory retina, the usual range of VA is from 0.25 to 0.05, averaging at 0.1.5 Approximately 34 percent of eyes with idiopathic macular holes show an increase in the lesion size, and 45 percent show a decrease in VA of two or more lines during a follow-up of several years.6 Generally, the vision loss stabilizes at the 0.1 to 0.05 level, and retinal pigment epithelial atrophy surrounding the macular hole occurs.12 Randomized clinical trials have reported that Stage 1 FTMHs with a baseline VA of 0.4 or worse showed a significantly higher risk of progression (66%) compared to Stage 1 macular holes with a baseline VA of 0.5 or better (33%).13 Most Stage 2 FTMHs, especially centric Stage 2 macular holes with pericentral hyperflourescence and eccentric holes, were found to progress to Stage 3 or 4.14 A spontaneous closure rate of the FTMHs has been described to occur in 11.5 percent of cases with a VA remaining stable.15

Treatment Options

Compared with observation alone, surgical intervention in Stage 2 macular holes result in a significantly lower incidence of hole enlargement and appear to be associated with a better functional outcome.16 Since the introduction of vitreous surgery followed by intraocular tamponade for the treatment of idiopathic FTMHs in 1991,

advances in vitreoretinal surgery resulted in a steady improvement of the anatomical and functional results.17 The current overall closure rate, as reported in a randomized clinical trial, is over 80 percent, with approximately 45 percent of eyes having a VA of 20/40 or greater. Additionally, surgical eyes present with a better near VA than observation eyes.15 Because the surgical outcome is influenced by the duration of symptoms, the preoperative macular function, and the preoperative hole diameter, early diagnosis and intervention in FTMHs should be emphasized.18 However, the benefit of vitrectomy for Stage 1 macular holes is still controversial.19,20 Patients with MPHs and LMHs usually have a favorable natural history with retaining a good VA, and surgery is only indicated for symptomatic ERM formation and/or vitreomacular traction and for decreasing VA to 0.25 level or less.21

ERMs are common in eyes with FTMHs. The presence of ERM does not correlate with postoperative VA, but excessive ERM growth contributes to hole reopening after surgery. Therefore, ERM peeling is recommended to be performed during surgery for FTMHs.22 A meta-analysis showed that removal of the ILM appears to significantly increase the anatomical, as well as the functional success rate in macular hole surgery.23 Other studies suggest that ILM peeling does not seem to be beneficial for macular holes less than 400µm in diameters.24 For better visualization and surgical manipulation, vital dyes for staining the ERM and/or the ILM have been introduced. Trypan blue (TB) and triamcinolone acetonide (TA) have proven to be effective and safe, and offer a favorable anatomic and functional outcome.25,26 Intravitreal application of indocyanine green (ICG) may cause retinal damage, resulting in less improvement of VA and unexpected visual field defects. The underlying mechanisms are still unclear and are the subject of ongoing investigations.25,27 To improve the hole closure rate, various biological adjuncts like transforming growth factor-β (TGFβ), autologous serum, thrombin, and autologous platelet concentrate have been introduced but not yet proven to have any added benefit compared to controls.15,28,29,30

After vitrectomy and membrane peeling, a intraocular tamponade is recommended for successful macular hole surgery. Perfluoropropane (C3F8) has proven to be a more effective tamponade than silicone oil with respect to initial closure rate and final VA in eyes with FTMHs.31 Additionally, long-acting gas tamponade (C3F8) gives a higher success rate compared to short-acting gas tamponade (SF6).

Fig. 13.1 Comparison of three optical coherence tomography (OCT) technologies for the evaluation of full-thickness macular holes (FTMHs)—FTMH Stage 4. The patient is a 77-year old man who presented a best corrected baseline visual acuity (VA) of 0.1 in the left eye. (a) The standard resolution Stratus OCT 3000 image (Zeiss) demonstrates a full-thickness macular hole with intraretinal cystic changes and irregularities in the photoreceptor layer. The posterior hyaloid is detached and an epiretinal membrane (ERM) is visible. (b) The ultrahigh resolution OCT (UHROCT), according to Drexler W et al., allows an improved visualization and structural analysis of the intraretinal changes. Additionally, the UHR-OCT shows irregularities in the inner and outer segments of the photoreceptor layer. (c) The three-dimensional UHR-OCT (3D UHR-OCT) image, according to Glittenberg C. et al, is comparable with a virtual biopsy. The photoreceptor inner and outer segments are clearly delineated in configuration and size, with a characteristic peak in the subfoveal area. The architecture of choroidal vascularization is distinctly imaged.

Postoperative face-down positioning is considered to be essential for short-acting gas, while the significance of posturing remains uncertain for long-acting gases.32 Complications of vitreoretinal surgery for FTMHs include a reopening of holes (2%), cystoid macular edema (1%), choroidal neovascular membrane (1%) and endophthalmitis in (1%). More common surgical complications are retinal pigment epithelium alterations in 33 percent of the cases and retinal detachment in 11 percent, which result in a significantly reduced postoperative VA.33 Therefore, the vitreoretinal procedure should be followed by a careful examination of the peripheral retina— particularly the sclerotomy incisions—to detect iatrogenic retinal tears and avoid entry site retinal detachments. Because of the high incidence of significant cataract formation after surgery, most surgeons perform a combined cataract surgery and vitrectomy. Combined surgery for FTMHs is a safe and effective procedure, allows for better intraoperative visualization, facilitates the use of a large gas bubble (which may contribute to hole closure without postoperative prone posturing), and

prevents patients from having to return for cataract surgery.34

The treatment of FTMHs continues to evolve because modifications to the standard surgical procedure have been proposed and evaluated. These innovations include sutureless 25-gauge and 23-gauge vitrectomy systems, the introduction of novel intraocular dyes, and the use of macular-protecting, yellow-tinted intraocular lenses for combined surgery.35,36,37,38 There is still no gold standard in macular hole surgery and some surgical procedures are controversial, including the benefit of ILM peeling, the use of ICG, and the details of endotamponades and post-operative positioning. Advances in OCT technology provide promising objective methods for analyzing morphological and functional aspects of idiopathic macular holes. The UHR-OCT and the three-dimensional UHR-OCT may help to elucidate all structural changes associated with macular holes, as well as improve early diagnosis, monitoring of disease progression, and response to treatment. The longer imaging times of these new diagnostic tools have to be refined, however, to make them applicable for the routine clinical setting.

References

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2.Smiddy WE, Flynn HW, Jr (2004) Pathogenesis of macular holes and therapeutic implications. Am J Ophthalmol 137:525-537

3.Schumann RG, Schaumberger MM, Rohleder M, et al. (2006) Ultrastructure of vitreomacular interface in full-thickness idiopathic macular hole. A consecutive analysis of 100 cases. Am J Ophthalmol 141:1112-1119

4.Lo WR, Hubbard GB (2006) Macular hole formation, spontaneous closure, and recurrence in a previously vitrectomized eye. Am J Ophthalmol 141:962-964

5.Ezra E (2001) Idiopathic full thickness macular hole: natural history and pathogenesis. Br J Ophthalmol 102-108

6.Chew EY, Sperduto RD, Hiller R, et al. (1999) Clinical course of macular holes: The Eye Disease Case-Control Study. Arch Ophthalmol 117:242-246

7.Gass JD (1995) Reappraisal of biomicroscopic classification of stages of development of macular hole. Am J Ophthalmol 119:752-759

8.Guez JE, Le Gargasson JF, Massin P, et al. (1998) Functional assessment of macular hole surgery by scanning laser ophthalmoscopy. Ophthalmology 105:694-699

9.Framme C, Roider J (2001) Fundus autofluorescence in macular hole surgery. Ophthalmic Surg Lasers 32:383-390

10.Ko TH, Fujimoto JG, Duker JS, et al. (2004) Comparison of Ultrahighand standard-resolution optical coherence tomography for imaging macular hole pathology and repair. Ophthalmology 111:2033-2043

11.C. Glittenberg, B. Povazay, B. Hermann (2007) Three dimensional reconstruction of tomographic images of the retina. Spektrum Augenheilkd 21:13-16

12.Casuso LA, Scott IU, Flynn HW, et al. (2001) Long-term follow-up of unoperated macular holes. Ophthalmology 108:1150-1155

13.Kokame GT, de Bustros S (1995) Visual acuity as a prognostic indicator in stage 1 macular holes. The Vitrectomy for Prevention of Macular Hole Study Group. Am J Ophthalmol 112-114

14.Kim JW, Freemann WR, el-Haig W, et al. (1995) Baseline characteristics, natural history and risk factors to progression in eyes with stage 2 macular holes. Results from a prospective randomized clinical trial. Vitrectomy for Macular Hole Study Group. Ophthalmology 102:1818-1828

15.Ezra E, Gregor ZJ (2004) Surgery for idiopathic full-thickness macular hole: Two-year results of a randomized clinical trial comparing natural history, vitrectomy and vitrectomy plus autologous serum: Moorfields Macular Hole Study Group Report No.1. Arch Ophthalmol 122:224-236

16.Kim JW, Freeman WR, Azen SP, et al. (1996) Prospective randomized trial of vitrectomy or observation for stage 2 macular holes. Vitrectomy for Macular Hole Study Group. Am J Ophthalmol 605-614

17.Kelly NE, Wendel RT (1991) Vitreous surgery for idiopathic macular holes. Results of a pilot study. Arch Ophthalmol 109:654-659

18.Kang SW, Ahn K, Ham DI (2003) Types of macular hole closure and their clinical implications. Br J Ophthalmol 87:1015-1019

19.De Butros S (1994) Vitrectomy for prevention of macular holes. Results of a randomized multicenter clinical trial. Vitrectomy for Prevention of Macular Hole Study Group. Ophthalmology 101:1055-1059

20.Subramanian ML, Truong SN, Rogers AH, et al. (2006) Vitrectomy for stage 1 holes identified by optical coherence tomography. Ophthalmic Surg Lasers Imaging 37:42-46

21.Smiddy WE, Gass JD (1995) Masquerades of macular holes. Ophthalmic Surg 26:16-24

22.Cheng L, Azen SP, El-Brady MH (2002) Effects of preoperative and postoperative epiretinal membranes on macular hole closure and visual restoration. Ophthalmology 109:1514-1520

23.Mester V, Kuhn F (2000) Internal limiting membrane removal in the management of full-thickness macular holes. Am J Ophthalmol 769-777

24.Tadayoni R, Gaudric A, Haouchine B, et al. (2006) Relationship between macular hole size and the potential benefit of internal membrane peeling. Br J Ophthalmol 90:1239-1241

25.Beutel J, Dahmen G, Ziegler A, et al. (2007) Internal limiting membrane peeling with indocyanine green or trypan blue in macular hole surgery: a randomized clinical trail. Arch Ophthalmol 125:326-323

26.Karacorlu M, Ozdemir H, Karacorlu A (2005) Does intravitreal acetonide-assisted peeling of the internal limiting membrane effect the outcome of macular hole surgery? Graefe’s Arch Clin Exp Ophthalmol 243:754-757

27.Gass CA, Haritoglou C, Schaumberger M, et al. (2003) Functional outcome of macular hole surgery with and without indocyanine green-assisted peeling of internal limiting membrane. Graefe’s Arch Clin Exp Ophthalmol 241:716-720

28.Duker JS, Wendel R, Patel AC, et al. (1994) Late re-opening of macular holes after initially successful treatment with vitreous surgery. Ophthalmology 101:1373-1378

29.Vine AD, Johnson MW (1996) Thrombin in the management of full-thickness macular holes. Retina 16:474-478

30.Korobelnik JF, Hannouche D, Belayachi N, et al. (1996) Autologous platelet concentrate as an adjunct in macular hole healing: a pilot study. Ophthalmology 103:590-594

31.Tafoya ME, Lambert HM, Vu L, et al. (2003) Visual outcomes of silicone oil versus gas tamponade for macular hole surgery. Semin Ophthalmol 18:127-131

32.Szurman P, Di Tizio FM, Lafaut B, et al. (2000) Significance of postoperative face-down positioning after surgery for idiopathic macular holes: consecutive case-control study. Klin Monatsblatt Augenheilkd 217:351-355

33.Banker AS, Freeman WR, Kim JW (1997) Vision-threatening complications of surgery for full-thickness macular holes. Vitrectomy for Macular Hole Study Group. Ophthalmology 104:1442-1452

34.Simcock PR, Scalia S (2001) Phacovitrectomy without prone posture for full-thickness macular holes. Br J Ophthalmol 85:1316-1319

35.Schuettauf F, Haritoglou C, May CA, et al. (2006) Administration of novel dyes for intraocular surgery: an in vivo toxicity animal study. Invest Ophthalmol Vis Sci. 47:3573-3578

36.Kellner L, Wimopissinger B, Stolba U, et al. (2007) 25-gauge versus 20-gauge system for pars plana vitrectomy: a prospective randomized clinical trial. Br J Ophthalmol Jan 3 (Epub ahead of print)

37.Rizzo S, Belting C, Cresti F, et al. (2007) Sutureless 25-gauge vitrectomy for idiopathic macular hole repair. Graefe’s Arch Clin Exp Ophthalmol Mar15 (Epub ahead of print)

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pathophysiology and surgical outcome of idiopathic macular holes is still not well-defined.4

ERMs arise from proliferation of glial cells on the inner retinal surface. The formation of the ERM is related to migration of astrocytes through breaks in the internal limiting membrane. The membranes are also composed of retinal pigment epithelium cells, fibrocytes, and myofibroblasts.5 Besides, investigations of the ultrastructure of the vitreoretinal interface in the vitreomacular traction syndrome suggest two different forms of epiretinal fibrocellular proliferation, namely ERMs interposed in native vitreous collagen as well as cell proliferation directly on the internal limiting membrane (ILM). A predominance of myofibroblasts may explain a high prevalence of cystoid macular edema and progressive vitreomacular traction characteristics for this disorder.6 According to Gass,7 translucent membranes without retinal distortion are classified as grade 0 (cellophane maculopathy), membranes with irregular wrinkling of the inner retina are classified as grade 1 (crinkled cellophane maculopathy), and membranes with distortion of the retinal vasculature are classified as grade 2 (macular pucker). The grading system adopted from Klein et al.8 divides ERMs into the relatively mild form without visible retinal folds (cellophane macular reflex), and the more severe form with retinal folds (preretinal macular fibrosis). However, no standard nomenclature is used at present, and ERMs are commonly classified according to their density, the severity of retinal distortion, and associated biomicroscopic changes.

ERMs have been reported to be slowly progressive and to rarely cause a severe visual impairment. Effects on vision vary depending on the severity and extent of the membrane. Patients with a mild ERM usually report no symptoms or may notice mild metamorphopsia like blurred or distorted vision, while a central photopsia often indicates traction on the macular area. If the ERM progresses to severe macular pucker, the central vision is affected.9 Occasionally, in less than 1 percent of cases, an ERM spontaneously separates from the retina, which may result in visual improvement.

Diagnostic Tools

The clinical examination of ERMs includes near and distance visual acuity testing, and evaluation of metamorphopsia with the standard Amsler grids and funduscopy. In the last few years, the optical coherence tomography (OCT) has become a standard diagnostic tool for preoperative and postoperative evaluation of ERMs. The OCT allows visualization of the full extent and localization of structural changes, as well as vitreoretinal adhesion or traction of ERMs. The main diagnostic characteristics for ERMs using the OCT are: 1) the ERM is separated or adherent, 2) a loss of the foveal depression, 3) a diffuse swelling of the retina, and 4) the presence of intraretinal cystic spaces. The OCT is highly specific and highly sensitive for measurements of the foveal thickness and for the structural assessment of the macula. OCT findings have shown that ERMs are more frequently fully adhered, rather than separated with focal points of adherence.