Focus on the macula

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Idiopathic epiretinal membrane
Case 1

A male Asian patient aged 66 was seen a few weeks after he purchased varifocal spectacles. His vision had deteriorated from 6/5 in the left eye to 6/9. Biomicroscopic examination revealed fine epiretinal membrane (ERM) at the fovea, which was responsible for the visual acuity drop. He was referred to an eye specialist with our findings.

A year later the patient was seen for a routine eye test and he was disappointed that no action was taken with regards to his symptoms. His visual acuity had in fact deteriorated to 6/18 and the epiretinal thickening appeared much worse on slit-lamp biomicroscopic examination and with fundus photography. Fundus imaging revealed a thickened and fibrosed epiretinal membrane distorting the blood vessels and centrally there appeared a psuedohole or macular pucker.

We also carried out an OCT examination at this visit and the effect on the macula was fairly devastating, with a much thickened central retina due to the epiretinal membrane (Figure 1). There was also a fibrous tuft of epiretinal membrane on the nasal side pulling on the macula which was visible on the OCT scan and the rest of the retina had the thickened epiretinal membrane but with much less traction. In fact, the radial scan on the OCT shows the very thickened membrane pulling from the nasal side and this traction has caused the macula to thicken and all the fine detail that we normally see at the macula is not evident any more. The OCT thickness map inside a 5mm grid shows that the central macula is thickened by at least 450 microns and this is illustrated by fovea, parafovea and perifovea being thick and colour-coded red. Our patient wanted a second opinion and he was referred to a vitreo-retinal specialist to see whether vitrectomy and membrane peel would be feasible.

Pathopathology of ERM

Epietinal membrane is the most common of the macular surface disorders and in most cases it is idiopathic. It is associated with posterior vitreous detachment and occurs in 12 per cent of elderly patients. Most ERMs are non-progressive and surgery is only indicated for cases that have clinically significant visual loss.

Slit-lamp biomicroscopy and fundus photography will show a glistening, yellow reflective membrane revealing a psuedohole due to contraction of the epiretinal membrane, creating a steep drop-off around the fovea.

ERMs are thought to be due to a proliferation of glial cells on the inner retinal surface. The inner limiting membrane acts as a scaffold for cellular proliferation and the push and pull effect of this fibrous tissue wrinkles the retina just like one would observe with crinkling of a cellophane wrapper.

Tractional cystoid macular oedema
Case 2

A 78-year-old male white patient was referred by his surgeon for an OCT examination of his left eye. He had cataract extraction in the left eye three months previously and, unfortunately, there was no improvement in his visual acuity post operation. His right eye was lost five years earlier with wet maculopathy.

His visual acuity was 6/24 and fundus examination with Volk 60D lens revealed macular oedema, but the fundus picture was less conclusive. OCT examination showed epiretinal membrane overlying the macular area together with cystoid changes in the foveal region (Figure 2). There were five cystoid spaces in the foveal and perifoveal area. The thickness map revealed macular thickness of 494 microns compared to 260 microns which is an average central macular thickness.

Diagnosis

The patient was diagnosed as having cystoid macular oedema (CMO) following cataract surgery and was referred back to his surgeon to see if anti-inflammatory eyedrops such as Acular and Diamox tablets would help.

Pathopathology of CMO

Cystoid macular oedema is clinically seen in 1-2 per cent of patients following cataract surgery and usually makes an appearance six weeks following surgery. OCT and flourescein angiography are useful in confirming CMO. The OCT reveals cystoid spaces within the perifoveal area and flourescein angiography would reveal a classic petalloid pattern of cystoid macular oedema.

Macular oedema is a result of excessive fluid within the layers of the retina itself. The osmotic and hydrostatic pressures between the retina and the retinal vessels maintain the amount of fluid within the outer plexiform (Henle's fibre) layer and the inner nuclear layer of the macula. A breakdown in the retina and blood vessel barrier allows fluid to accumulate in cystoid spaces within the retina.

Two mechanisms proposed

• The chronic inflammation mechanism postulates that mediators such as prostaglandins are released in the eye. This theory is supported by reduction in the oedema with non-steroidal anti-inflammatory drugs and cyclooxygenase inhibitors
• The tractional mechanism theory advocates a disruption in the vitreo-retinal interface. Local forces also induce a release of mediators that lead to retinal and blood vessel barrier breakdown.

Treatment of CME is with anti-inflammatory drugs such as Acular and occasionally combined with Diamox. In some instances laser photocoagulation is undertaken for cystoid macular oedema.

Idiopathic macular hole
Case 3

A white woman aged 67 was referred by an eye specialist for a second opinion on her right eye which had undergone Avastin treatment three months ago following wet maculopathy in that eye six months previously. Unfortunately, there were no pictures or scans or fluorescein images available to us. Her visual acuity at the visit was count fingers in the right eye and 6/24 in the left eye. Both eyes on fundus imaging and Volk lens examination showed a black clump of deposits on the pigment epithelium but no obvious signs of cystoid maculopathy. Due to the black deposits on the right central area it was very difficult to view the fovea.

Fortunately, with the fundus image we were able to zoom into this central area and with precision scanning we were able to ascertain a tiny red spot, indicating a possible hole in the centre. Yellow deposits were not apparent in the centre and there were no signs of a halo of retinal detachment surrounding this hole.

OCT examination was quite remarkable, showing deposits on the pigment epithelium on the centre of both fovea which is indicated by thickened red pigment epithelium (Figure 3). The right fovea when observed in great detail revealed what appeared to be a macular hole with a diameter of 329 microns at the base. There was slight cystoid change either side but no true signs of wet maculopathy, indicating that the treatment with anti-VEGF intra-vitreal injections was successful.

Her thickness map (Figure 4) was interesting, revealing a depressed fovea plotted in blue with a thickened retina in the surrounding area. This is an illusion, as the central area is thin it makes the surrounding retina appear thicker. The fovea was roughly 40 microns thinner in the right eye.

Diagnosis

The patient was told that she had a possible macular hole and was referred back to the treating specialist with a recommendation of a further referral to a vitreo-retinal surgeon to see whether any surgical intervention would help. Her macular hole was noted as a stage 2 and considering the size and the drop in visual acuity it really should be classified as a stage 3 hole. She was also reassured that her maculopathy treatment was successful and unfortunately an unforeseen complication arose in the form of a macular hole. The retinal pigment epithelium clumping seen in both eyes could be due to age-related macular degeneration or it could also be associated with repeated central serous retinopathy and resolution following the episodes of CSR.

Pathopathology of idiopathic macular hole

Macular hole is a defect of the foveal retina involving the internal limiting membrane to the outer segments of the photoreceptor layer and not involving the retinal pigment epithelium. The incidence of macular hole is 0.03 per cent to 0.05 per cent of the population with a 3:1 female to male ratio and the peak incidence in the seventh decade.

Patients experience symptoms of central scotoma, decreased acuity and/or metamorphosia. Visual acuity can range from 6/12 to counting fingers.

Mechanisms of macular hole are diverse including hormonal variation, systemic vascular disease, chronic oedema, solar retinopathy and blunt trauma to mention a few. Vitreo-macular traction and fluid flow theories are recognised theories for macular hole formation.

The vitreo-macular traction is due to pre-foveal vitreous shrinkage and the traction is predominantly anterior-posterior (A-P) in direction.

The fluid flow theory suggests that fluid flow is initiated by macular retinal pigment epithelial pump leading to hole formation. With the lack of operculum on the OCT scan this theory gains credence in our case. This patient, as we noted, had wet maculopathy and the likelihood of cystoid maculopathy. Anti-vascular endothelial growth factor treatment would have had an effect on the fluid within the retina.The treatment probably stimulated the fluid flow out of the thickened fovea. This sudden fluid movement could have led to the collapse in the central fibre layout leading to hole formation?

J Donald M Gass developed a macular hole grading system from the understanding of a temporal association between posterior vitreous detachment and full thickness macular hole. The four stages of macular hole described by Gass are:

• Stage 1a and 1b - presence of a foveal detachment and a yellow central spot size 250-300 microns. The yellow appearance is due to fovealar detachment which reveals the intra-retinal pigment xanthophyll. In stage 1b the hole gets bigger and there is a loss of foveal depression
• Stage 2 - there is a partial thickness hole having a size less than 400 microns. At this stage there is an actual retinal dehiscence ie early macular hole
• Stage 3 - appearance of a red central area of diameter greater than 400 microns and less than 500 microns. It is accompanied by a rim of retinal elevation with or without an operculum
• Stage 4 - an advanced full thickness 500 micron or greater macular hole with a halo of retinal detachment surround. This stage is associated with a complete posterior vitreous detachment (Figure 5).

Prognosis of macular hole

• 50 per cent chance that stage 1 macular hole will be self-limiting
• 50 per cent of stage 1 hole will progress to stage 2 and in this instance vitrectomy would help prevent progression to stage 2 and help improve vision
• 70 per cent of stage 2 will progress to stage 3 and again vitrectomy would be helpful to preserve vision
• 50 per cent chance that the second eye will be involved.

Further reading

1. llen AW jr, Gass JD. Contraction of a perifoveal epiretinal membrane simulating a macular hole. Am J Ophthalmol, 1976 Nov 82(5): 684-691.
2. Azzolini C, Fatelli F, Brancato R. Correlation between optical coherence tomography and biomicroscopic interpretation of idiopathic macular hole. Am J Ophthalmol, 2001 Sept 132(3): 348-355.
3. Bovino JA, Kelly TJ, Marcus DF. Intraretinal haemorrhages in cystoid macular oedema. Arch Ophthalmol, 1984 102: 1151-52.
4. Chan A, Ducker JS, Schuman JS, et al. Stage 0 macular holes observations by optical coherence tomography. Ophthalmology, 2004 Nov 111(11): 2027-32.
5. Der Bustros S. The vitrectomy for the prevention of macular hole study group : Vitrectomy for prevention of macular holes : results of a randomised multicenter clinical trial. Ophthalmology, 1994 101: 1055-59.
6. Federman JL, Gouras P, Schubert H, Slusher MM, et al. Macular disorders. In: Podos SM, Yanoff M, eds. Retina and vitreous. Textbook of ophthalmology, Vol 9 1994: 15-17.
7. Foos RY, Wheeler NC. Vitreoretinal juncture. Synchysis senilis and posterior vitreous detachment. Ophthalmology, 1982 Dec 82(12) : 1502-12.
8. Fung WE. Retina. In: other causes of cystoid macular oedema and retinal trauma after surgery. 2(2) 1994: 1811-17.
9. Gallemore RP, Jumper JM, Mc Cuen BW 2nd et al. Diagnosis of vitreoretinal adhesions in macular disease with ocular coherence tomography. Retina, 2000 20(2):115-20.
10. Gandorfer A, Rohleder M, Kampik A. Epiretinal pathology of vitreomacular traction syndrome. Br J Ophthalmol, 2002 Aug 86(8) : 902-9.
11. Gass JDM. Idiopathic senile macular hole. Its early stages and pathogenesis. Arch Ophthalmol, 1998 106: 629-39.
12. Gass JDM. Stereoscopic atlas of macular disease, 2nd ed. St. Louis: cv Mosby 1977 346-348.
13. Gribromont AC. Surgical prognosis in idiopathic vitreomacular syndrome and epiretinal membrane. J Fr Ophthalmol, 2005 Sept 28(7): 739-742.
14. Guyer DR, Gragoudas ES : Idiopathic macular holes. In: Albert DN, Jackobiec FA, eds. Principles and practice of ophthalmology, 1994 883-888.
15. Haquchine B, Massin P, Gandric A. Foveal psuedocyst as the first step in macular hole formation. Ophthalmology, 2001 Jan 108(1): 15-22.
16. Hikichi T, Takashi M, Trempe CL, Schepens CL. Relationship between premacular cortical vitreous defects and idiopathic premacular fibrosis. Retina, 1995 15: 413-416.
17. Johnson MW. Tractional cystoid macular edema: a subtle variant of the vitremacular traction syndrome. Am J Ophthalmol, 2005 Aug 140(2): 184-92.
18. Johnson RW, Gass JDM. Idiopathic macular holes. Observations, stages of formation, and implications for surgical intervention. Ophthalmology, 1988 95: 917-924.
19. Kishi S, Schimizu K. Oval defect in detached posterior hyaloid in idiopathic preretinal macular fibrosis. Am J Ophthalmol, 1994 118: 451-456.
20. Korner F, Garweg J. Diseases of the vitreo-macular interface. Klin Monatsbl Augenheilkd, 1999 May 214(5): 305-310.
21. Kusaka S, Saito Y, Okada AA, et al. Optical coherence tomography in spontaneously resolving vitreomacular traction syndrome. Ophthalmologica, 2001 Mar-Apr 215(2): 139-141.
22. McDonald HR, Johnson RN, Schatz H. Surgical results in vitreomacular traction syndrome. Ophthalmology, 1994 101: 1397-1403.
23. McDonnell PJ, Ryan SJ, Walonker AF, Miller-Scholte. A prediction of visual acuity recovery in cystoid macular edema. Ophthalmic surg, May 1992 23(5): 354-8.
24. Munuera JM, Garcia-Lavana A, Maldonado MJ, et al. Optical coherence tomography in successful surgery of vitreomacular traction syndrome. Arch Ophthalmol, 1998 Oct 116(10) : 1388-9.
25. Ray S, D'Amico DJ. Psuedoaphakic cystoid macular edema. Semin Ophthalmol, 2002 Sept-Dec 17(3-4) : 167-180.
26. Rodriguez A, Infante R, Rodriguez FJ, Valencia M. Spontaneous separation in idiopathic vitreomacular traction syndrome associated with contralateral full thickness macular hole. Eler J Ophthalmol, 2006 Sept-Oct 16(5) : 733-740.
27. Roth AM, Foos RY. Surface wrinkling retinopathy in eyes ennucleated at autopsy. Trans Am Acad Ophthalmol Otolaryng, 1971 75: op 1047.
28. Sebag J. Age-related differences in the human vitreoretinal interface. Arch Ophthalmol, 1991 109 : 996-971.
29. Senoda K, Sakamoto J, Enaida M, Miyazaki M, Noda Y, Nakamura T, Ueno A, Yokoyama M, Kubota T, Ishibashi T. Residual vitreous cortex after surgical posterior vitreous separation visualised by intravenous triamcinolone acetonide. Ophthalmology, volume 111, issue 2, pages 226-230.
30. Smiddy WE, Michels RE, Green WR. Morphology, pathology and surgery of idiopathic vitreoretinal macular disorders. A review. Retina, 1990 10(4) 288-96.
31. Wendel RT, Patel AC, Kelly NE, Salzano TC, Wells JW, Novack GD. Vitreous surgery for macular holes. Ophthalmology, 1993 100: 1671-1676.

? Kirit Patel works in private practice in Radlett