Surgical Management of Subfoveal Choroidal Neovascularization

Surgical Management of Subfoveal Choroidal N eovascularization Matthew A Thomas, MD, M. Gilbert Grand, MD, David F. Williams, MD, Carol M. Lee, MD, Samuel R. Pesin, MD, Marc A Lowe, MD Background: Subfoveal choroidal neovascularization (CNV) usually is associated with a poor visual prognosis. Laser photocoagulation of certain subfoveal membranes secondary to age-related macular degeneration (ARMD) appears preferable to observation based on recent Macular Photocoagulation Study (MPS) findings but is associated with decreased vision. The authors explored the use of vitreoretinal surgical techniques as an alternative method of eradicating subfoveal CNV. Methods: After vitrectomy, a small retinotomy technique was used to extract or disconnect from the choroidal circulation subfoveal CNV in 58 eyes. There were 33 eyes with ARMD, 20 eyes with presumed ocular histoplasmosis, and 5 eyes with miscellaneous etiologies. Five eyes also received subfoveal RPE patches. Results: With limited follow-up, significant improvement in vision (defined as 2 Snellen lines) was achieved in 7 of 22 eyes with ARMD CNV removal (1 eye 20/20), 0 of 4 eyes with ARMD CNV removal and RPE patches, and 1 of 7 eyes with ARMD CNV disconnection. Significant improvement was achieved in 6 of 16 eyes with presumed ocular histoplasmosis removal and 0 of 4 eyes with presumed ocular histoplasmosis CNV disconnection. In 5 eyes with miscellaneous CNV, 2 improved (20/20 and 20/40). CNV recurred in 29%. Conclusions: Some patients with subfoveal CNV appear to benefit from surgical removal. Only rarely do eyes with ARMD improve. Longer-term follow-up and refined case selection are required before this approach can be widely recommended. Ophthalmology 1992;99:952-968

Choroidal neovascularization (CNV) is an important cause of visual loss in a variety of macular conditions. 1 Vascular buds from the choroid grow through Bruch's membrane and proliferate beneath and/or above the ret-

Originally received: October 13, 1991. Revision accepted: January 8, 1992. From Retina Consultants, Ltd, St. Louis. Presented at the American Academy of Ophthalmology Meeting, Anaheim, October 1991. Supported in part by the Retina Research and Development Foundation, St. Louis, Missouri. The authors have no proprietary interest in the development or marketing of any instrument described in this study. Reprint requests to Matthew A. Thomas, MD, Suite 17413, East Pavilion, One Barnes Hospital Plaza, St. Louis, MO 63110.

952

inal pigment epithelium. Aging changes (as in age-related macular degeneration [ARMD]), postinflammatory changes (as in the presumed ocular histoplasmosis syndrome [POHS]), and other unidentified factors allow this vascular invasion to occur. Once through Bruch's membrane, the fibrovascular tissue, serous exudation and/or hemorrhage may degrade visual function? When fibrovascular membranes grow beneath the center of the foveal avascular zone (FAZ), the visual outlook is generally poor. Bressler and colleagues3 found that 70% of eyes with subfoveal membranes secondary to ARMD had acuities o:f 20/200 or worse within 2 years. Eyes with POHS may do better; as many as 14% may maintain visual acuity of 20/40 despite subfoveal vessels. 4 Fibrovascular membranes usually continue to grow without treatment. Vander and associates 5 documented an average growth rate of 9 ~-tm daily in eyes with neovascular membranes

Thomas et al · Subfoveal Choroidal Neovascularization and ARMD. Enlarging membranes beneath the fovea often lead to disciform scars with very poor visual function. Laser photocoagulation is the only treatment of proven benefit in eyes with choroidal neovascularization. The Macular Photocoagulation Study (MPS) has established the superiority oflaser treatment over observation for extrafoveal, juxtafoveal, and subfoveal vessels. 6- 13 When vessels extend beneath the center of the fovea, laser treatment may limit scotoma size, 14 but central visual function is reduced. Recently, the MPS group reported a positive treatment effect oflaser photocoagulation compared with no treatment for eyes with subfoveal choroidal neovascularization associated with ARMD. 12 Although treated eyes experienced an immediate reduction in acuity (average 3 lines), by 24 months, treated eyes had a smaller decrease in visual acuity than untreated eyes. A similar treatment benefit was established for recurrent subfoveal neovascular lesions. 13 Despite its documented advantages over observation, macular photocoagulation for choroidal neovascularization is not a panacea. 15 In the subfoveal study, most patients evaluated with subfoveal membranes did not meet the inclusion criteria. Two years after photocoagulation, the mean acuity of those treated was 20/320, and 82% had visual acuity of 20/200 or worse. 12 Recurrent neovascularization is frequent. According to MPS data, 52% of eyes with ARMD and 28% of eyes with POHS or idiopathic neovascularization that were treated for extrafoveal membranes had recurrent neovascularization within 24 months of treatment. 16 In parafoveal lesions treated with krypton red laser, recurrences were even more frequent: 66% of eyes with ARMD and 31% of eyes with POHS had persistent or recurrent neovascularization by 24 months after treatment. 17 •18 Most recurrences occurred on the foveal side of the membrane. Even the subfoveal photocoagulation group had a 24% incidence of persistent neovascularization within 6 weeks of treatment and a 32% incidence of recurrent neovascularization within 3 yearsY These high recurrence rates were seen despite treatment by experienced retinal specialists and despite careful postlaser scrutiny of the photocoagulation lesions with color photographs and fluorescein angiograms by the reading center as well as by the treating physician. 19 The poor natural history of subfoveal choroidal neovascularization and the limitations of laser photocoagulation prompted our search for alternative ways to manage this condition. We explored the use of vitreoretinal surgical techniques in subfoveal choroidal neovascularization. This report presents our surgical technique and early experience with surgical management of subfoveal neovascular membranes in 58 consecutive patients.

Patients and Methods Case Selection Patients of Retina Consultants, Ltd, St. Louis, Missouri, who were older than 21 years of age and who had subfoveal

choroidal neovascularization were evaluated for possible surgical intervention. This report summarizes a consecutive series of patients operated on for subfoveal neovascularization. Clinical examination with either contact lens, Hruby lens, or 78-diopter lens as well as fluorescein angiography were used to determine the presence of choroidal neovascularization beneath the center of the fovea. Fluorescein angiographic patterns varied. Inclusion required angiographic evidence of either a well-defined neovascular complex or, if the membrane was ill-defined, a pattern of increasing late hyperfluorescence consistent with neovascularization beneath the center of the FAZ. Patients were excluded if thick subretinal or sub-retinal pigment epithelium (RPE) blood was present. ("Thick" was defined as causing obvious elevation of the fovea on stereo photographs and/or binocular clinical examination, as described by Bennett et al. 20 ) Pigment epithelial detachments without definite evidence of neovascularization were excluded. Eyes with media opacities precluding a good view of the fundus were excluded. Any eyes that met MPS criteria for laser treatment of extrafoveal or juxtafoveal membranes were excluded from this study and received appropriate laser therapy. (The MPS results of laser treatment for subfoveal membranes were not available during the recruitment of patients reported here.) Observation without treatment, foveal laser photocoagulation, and vitreoretinal surgical intervention were presented as management options, and the unproven nature of the latter was candidly discussed. Written informed consent was obtained.

Surgical Technique In 1989, deJuan and Machemer21 reported 4 cases of submacular scar removal using vitrectomy techniques. More recently, Blinder, Peyman and colleagues described a technique for excision of submacular scars in ARMD 22 and a technique for transplantation of retinal pigment epithelium. 23 These surgeons used a large circumferential retinotomy around the macula to create a flap that is retracted to expose the subretinal space. As previously reported, we emphasize the creation of a small retinotomy eccentric to the fovea. 24 Surgical manipulation of the neovascular complex is accomplished by instruments introduced through the retinotomy and visualized through neurosensory retina. Three variations of the small retinotomy technique were used in this series of patients. Technique 1: Choroidal Neovascular Membrane Extraction. A frame of the fluorescein angiogram is selected that best delineates the neovascular membrane. In cases in which the membrane is predominantly anterior to RPE, an early arteriovenous phase frame is often most informative. In cases with late, increasing staining at the level of the RPE, sub-RPE neovascularization is presumed, and a later frame is chosen to appreciate the full extent of the membrane. 25 The frame is projected on a screen in the operating room, reversed and inverted to

953

Ophthalmology

Volume 99, Number 6, June 1992

match the surgeon's view through the microscope. After a complete vitrectomy, the posterior hyaloid is engaged by active aspiration through a silicone-tipped extrusion needle, 26 and the hyaloid is detached and subsequently excised. 27 •28 A retinotomy site is selected to gain access to the subretinal space. This is almost always placed just temporal to the fovea or temporal to the leading edge of the membrane. The specific configuration of the membrane or of pre-existing photocoagulation scars may occasionally dictate a different location. The tapered endodiathermy probe is used to coagulate the retinotomy site lightly. A small (approximately 200 J,tm) defect in neurosensory retina is created either by the diathermy tip itself or by gentle spreading with a myringotomy blade. A recently developed 20-gauge needle tapered to a blunt 30-gauge tip is attached via a short flexible tube to a 5-ml syringe filled with balanced salt solution. 29 An assistant very slowly injects the solution into the subretinal space while the surgeon directs the 30-gauge tip at the small retinal defect. This creates a shallow posterior pole neurosensory retinal detachment. An angled subretinal pick has been developed that allows manipulation in the subretinal space through the eccentric retinotomy? 9 The 4-mm tip tapers to 0.305 mm (narrower than 30 gauge) and is bent at an angle of 130° from the 20-gauge shaft. The 130° angle allows motion at the tip with less risk of striking underlying tissue at the retinotomy site with the heel of the instrument. The pick tip is used to push against or under the leading edge of the neovascular complex. In some cases, the membrane edge separates from underlying RPE. If such a cleavage plane can be established, then the tip of the pick is gently advanced and passed laterally, parallel to underlying RPE until the majority of the membrane is disconnected. One can usually feel, with the pick, a stalk of residual tissue connecting the posterior surface of the membrane to the choroid. In some cases, it is apparent that the neovascular complex is inseparably connected with underlying RPE and choriocapillaris and/or the membrane has multiple vascular connections from the choroid. 30 Pressure from the pick can break such a complex free from its choroidal connections, but an RPE defect is created behind the dislodged membrane. During any manipulations that risk fracturing choroidal vessels, the intraocular pressure is increased by raising the infusion bottles temporarily. New forceps have been designed for use in the subretinal space with horizontally opposing blades 2.4-mm long and angled 130° from the 20-gauge shaft. 29 These are introduced (closed) through the retinotomy, then opened and the trunk of the complex, or the complex itself, is grasped and extracted. In the majority of cases with preexisting laser photocoagulation scars, the fibrous laser scar remains connected to the recurrent subfoveal membrane, and the laser scar is delivered with the grasped membrane. The retinotomy usually enlarges slightly, but the retinal fibers stretch around the membrane as it is delivered, leaving a much smaller defect than the size of the mem-

954

brane itself. The subretinal space is carefully studied while the intraocular pressure is lowered; if any bleeding occurs, the pressure is quickly increased for another minute. An air-fluid exchange is then performed. The 30-gauge needle allows aspiration through the small retinotomy to collapse the neurosensory retinal detachment with less risk of incarcerating surrounding tissue than with larger caliber needles. 29 Photocoagulation lesions of minimal intensity are placed tightly around the retinotomy. Gas tamponade of the retinotomy is achieved with either sulfur hexafluoride or perfluoropropane and appropriate patient positioning until a chorioretinal adhesion can form. Technique 2: Choroidal Neovascular Membrane Disconnection without Removal. In some cases, the subretinal pick was used to disconnect the neovascular membrane from its choroidal connections without removing any subretinal tissue. In certain cases, as the pick was used to push against the edge of the neovascular complex, it was apparent that the underlying RPE was adherent to the membrane and would be extracted if the complex were removed. Because it was appreciated early in the series that eyes without foveal RPE had limited central vision, some of these eyes did not undergo membrane removal. Rather, the pick was used to dislodge the complex in hopes of disconnecting its vascular supply from the choroid. In other certain eyes, previous laser scars were firmly adherent to overlying neurosensory retina and precluded removal of the membrane/scar complex. In other cases, a dissection behind the neovascular complex was intentionally performed to avoid extracting subfoveal RPE. In these few cases, the neurosensory retina was not elevated; rather, after the retinotomy was created, the subretinal pick was introduced carefully through RPE and advanced behind the neovascular complex. Light from the endoillumination probe reflected from the metal surface of the pick as visualized through RPE. In certain cases, macroscopically visible vessels in the neovascular complex were seen in front of the pick, helping confirm that the pick had indeed passed behind not only RPE but behind the membrane as well. Once in this space, the pick tip was rotated superiorly and inferiorly until all connections with underlying choroid presumably had been severed. Technique 3: Membrane Removal with Placement of RPE Patch. In an attempt to improve the visual outcome in some eyes in which extraction of the neovascular complex had resulted in extraction of foveal RPE, RPE patches were placed beneath the fovea. Small patches (500 to 1000 J.tm in diameter) ofRPE/Bruch's membrane were dissected from surrounding RPE eccentric to the fovea and placed under the fovea. In one case, RPE (which was extracted from the subretinal space connected to the edge of the membrane) was cut free and repositioned under the fovea. In another case, vertical intraocular scissors were used to dissect a 1200 J,tm diameter patch of RPE/ Bruch's membrane/choriocapillaris from beneath the temporal retinotomy and this thick patch was positioned beneath the fovea.

Thomas et al · Subfoveal Choroidal Neovascularization Patients Patient data are presented in three groups based on the etiology of the choroidal neovascularization: ARMD, POHS, and miscellaneous causes.

Age-related Macular Degeneration Data from 33 eyes of 33 patients with ARMD who underwent surgery for subfoveal fibrovascular membranes are presented in Tables 1A, B, and C. Sixteen patients were male and 17 were female. Ages ranged from 59 to 87 years (average, 71.7 years). In 10 patients, macular photocoagulation had previously been performed. Preoperative visual acuities ranged from 20/30 to counting fingers at 2 feet. The patient with 20/30 visual acuity had been observed for several weeks with an enlarging subfoveal membrane and increasingly symptomatic metamorphopsia. Continued observation was advised, but the patient believed his vision was deteriorating significantly and strongly desired surgery. In 29 of 33 eyes (88% ), preoperative acuity was 20/200 or worse. The exact duration of subfoveal neovascularization was usually impossible to ascertain since most patients presented with subfoveal membranes and had not been recently examined before this presentation.

Presumed Ocular Histoplasmosis Syndrome Data from 20 eyes of 20 patients with subfoveal membranes secondary to POHS are presented in Tables 2A and B. Ages ranged from 22 to 68 years (average, 46.6 years), and there were 9 women and 11 men. In 10 ofthe 20 cases, subfoveal vessels developed after previous laser treatment. New vessels had been present beneath the fovea for more than 12 months in 2 eyes (cases 8 and 16) and for 6 months or less in 17. Preoperative visual acuities ranged from 20/30 to counting fingers at 2 feet. All but one of the eyes from which POHS membranes were removed had preoperative visual acuities of20/200 or worse. All of the eyes that subsequently underwent membrane disconnections had initial visual acuities of 20/100 or better.

Subfoveal Membranes of Other Etiologies Five additional patients with subfoveal membranes underwent surgery. Causes included: angioid streaks (2 eyes), idiopathic (2 eyes) and serpiginous choroiditis (1 eye). As shown in Table 3 and Figure I, preoperative visual acuities ranged from 20/200 to 20/800 by near card.

Results Age-related Macular Degeneration Membrane Removal (22 Eyes). Average postoperative follow-up was 7.8 months (range, 3 to 16 months)

(Table 1A) (Fig. 2). If significant visual change is defined as greater than or equal to two Snellen lines of change, and if the gradations of acuity are as listed in Figure 2, then 7 eyes improved significantly, 7 eyes worsened significantly, and 8 eyes remained unchanged. Only in one case was reading acuity restored (case 16, 20/20 visual acuity), and in 19 eyes (86%) final visual acuity was 20/ 200 or worse. In 21 of 22 cases, the membrane was removed entirely at the time of surgery. It was the impression of the surgeon that, in 18 of 22 eyes, subfovea1 RPE was extracted with the complex. In four eyes, foveal RPE was present postoperatively but abnormal in appearance. Eight of 22 eyes (36%) had either persistent or recurrent neovascularization occurring from 1 to 12 months after surgery (average, 5 months). These vessels recurred in or at the edge of the RPE defect or disturbance created at the time of surgery.

Case Reports Age-related Macular Degeneration Case 1. An 87year-old woman had a disciform scar with visual acuity of counting fingers at 3 feet in the left eye and a large subfoveal membrane with 20/200 visual acuity in the right (Fig 3). As the first patient to undergo extraction of a subfoveal membrane, she received a larger temporal retinotomy than was found to be necessary in subsequent cases. A thick, fibrotic plate of tissue was peeled off the undersurface of the retina and demonstrated the tensile strength of choroidal neovascular membranes, the absence of hemorrhage on removal, and their larger size than that appreciated angiographically. The majority of the tissue was composed of a basement membrane-like material, presumably elaborated by RPE cells (Fig 4). Alcian blue stains and electron microscopy confirmed the predominance of the basement membrane material and immunoperoxidase staining identified collagen type IV as the predominant collagen present. All subsequent specimens had similar cellular and extracellular matrix components. Postoperatively, foveal RPE was absent, and visual acuity decreased slightly to 20/400. With 13 months offollow-up, visual acuity remained stable (Fig 5). Age-related Macular Degeneration Case 16. A 68-

year-old woman presented with a longstanding macular hole and visual acuity of counting fingers in the left eye and a 2month history of blurred vision in the right. Acuity had been measured by the referring ophthalmologist as 20/200 in the right eye on several visits. Immediately preoperatively in our office, best-corrected acuity measured 20/80 in the right eye, and the angiogram demonstrated a choroidal neovascular membrane lying mostly temporal to the foveal avascular zone, but with extension under the center of the fovea (Figs 6 and 7). Intraoperatively, an RPE defect was created beneath the temporal aspect of the neovascular complex, but the nasal aspect of the membrane appeared to pull free with minimal disturbance of underlying foveal RPE (Fig 8). Two months later, visual acuity had improved to 20/20 (Fig 9). At 3 months after surgery, a juxtafoveal recurrent membrane developed and was treated with krypton laser. At last follow-up, 9 months after surgery, visual acuity remained 20/20.

Age-related Macular Degeneration Case 7. A 67-

year-old woman with a disciform scar and visual acuity of

955

Ophthalmology

Volume 99, Number 6, June 1992

Table 1. Age-related Macular Degeneration Case No.

Age (yrs)

Sex

Preoperative Visual Acuity

Best Postoperative Visual Acuity

No No No

20/200 CF 2' 20/30

No

20/300

20/400 20/800 NC 20/50 at 3 mos 20/80 at 6mos

Previous Laser

Final Visual Acuity

Follow-up (mos)

20/400 20/800 NC

13 13

Foveal

RPE

CNVM Recurrence

Comments

Table lA. ARMD Removal

2

87 75

F F

3A

59

M

1

3B

Reoperation

5

Absent Absent Absent

0 0 5 mos

20/200

11

Absent

9mos

20/200 20/200 20/200

13

7 mos

11

Absent Absent Absent

0 1 and 4 mos

20/100

12

Absent

12 mos

20/400

6

20/200 20/400NC 20/400

9 3

4

84

F

5

77

6

64

M M

No No Yes

20/100 20/400 20/400

7

67

F

Yes

20/400

8

60

M

No

20/200

9 10 11

71 81 63

M F F

Yes No No

20/200 20/400 20/300

20/200 20/200 20/100 at 2 mos 20/70 at 11 mos 20/200 at 3 mos 20/200 20/400 NC 20/400

12 13

72 77

14

64

M F M

Yes Yes No

20/60 20/400 20/200

20/200 20/800 NC 20/200

20/200 20/800 NC 20/200

15 16

62 68

F F

No No

20/300 20/80

20/400 20/20

20/400 20/20

6 9

Persistent CNVM Absent Absent Present Abnormal Absent Absent Present Abnormal Absent Present

17

82

F

No

20/200

20/400

20/400

5

Absent

0

18

74

M

Yes

20/400

20/200

20/200

5

0

19 20

69

73

M M

Yes No

20/400 NC 20/300

20/100 20/200

20/100 20/200

3 3

Present Abnormal Absent Absent

21

78 75

F F

No No

CF2' 20/400

20/800 NC 20/200

20/800 NC 20/200

3 3

Absent Absent

0 0

22

12

7

10 6

4

Second recurrence lasered 20/80 acuity dropped to 20/200

Persistent 0 5 mos 0 0 0 0

0 3 mos

0 0

Juxtafoveal recurrence lase red CNVM adherent toNS retina

Large CNVM with exudate, RD resolved Postoperative RD Large exudative RD resolved

Table lB. ARMD Membrane Disconnections 23

77

M

No

20/50

20/200

20/300

8

Present

0

24

73

F

No

20/800 NC

20/200

6

Present

0

25 26

66 74 69

28 29

67 77

No No Yes Yes Yes

20/400 NC 20/200 20/200 20/300 20/200

20/400 NC 20/200 20/100 20/100 20/200

3 3

27

M M F M F

20/100 at 2 mos 20/400 NC 20/200 20/100 20/100 20/200

Present Present Present Present Present Abnormal

11

Patch

0

7

Patch

0

4 3 3

Postoperative laser surrounding fovea

0 0 3 mos 3 mos 0

Table lC. ARMD RPE Patches 30

72

F

No

CF 5'

20/300

20/800 NC

31

78

M

No

20/200

20/300

20/200

956

Small RPE patch, contracted Small RPE patch, contrasted

Table 1 (continued) Case No.

Age (yrs)

Sex

Previous Laser

Preoperative Visual Acuity

Best Postoperative Visual Acuity 20/200 at 3 mos 20/200 at 2 mos

Final Visual Acuity

Follow-up (mos)

20/400 NC

8

Patch

3 mos

20/800 NC

7

Patch

0

CNVM Recurrence

Foveal RPE

Comments

Table 1C. ARMD RPE Patches 32

82

M

No

20/200

33

79

F

No

20/200

Small RPE patch, contracted Large RPE/ Bruch's membrane/ choriocapillaris patch, contracted

ARMD = age-related macular degeneration; CF = counting fingers; NC = near card; CNVM = choroidal neovascular membrane; RD = retinal detachment; RPE = retinal pigment epithelium; NS = neurosensory.

Table 2. Presumed Ocular Histoplasmosis Syndrome Case No.

Age (yrs)

Sex

Previous Laser

Preoperative Visual Acuity

Best Postoperative Visual Acuity

Final Visual Acuity

Follow-up (mos)

Foveal RPE

20/100

5

Persistent

20/70 20/300

8 8

Present Abnormal Abnormal Abnormal

20/200 20/50

3 4

0 4mos

CNVM Recurrence

Comments

Table 2A. POHS Membrane Removal 1A 1B

2

42

M

Reoperation 22 F

No

20/300

No

CF 3' 20/80

No No

20/200 20/200

20/60 at 2 mos 20/70 20/100 at 3 mos 20/60 at 1 mo 20/50

Yes

20/200 20/200

20/200 20/60

20/200 20/60

3 5

5 mos 4mos

6

51

M

No

CF2'

20/400

20/400

7

7

44

F

Yes

20/300

20/200

20/200

4

Present Present Abnormal Absent Present Abnormal Present Abnormal Present

8 9

50 62

M F

No Yes

20/300 20/200

20/300 20/60 at 2 mos

20/300 20/200

5 4

Absent Present

0 3 mos

10 11 12

39 66 50

F F M

Yes No No

20/200 20/400 20/800 NC

20/200 20/400 20/200

4 3 3

Absent Present Present

0 0 3 mos

13

14

41 39

F F

Yes Yes

20/200 20/200

20/200 20/400 20/80 at 2 mos 20/100 20/25

20/100 20/50

3 2

15

44

M

Yes

20/400

20/200

20/200

2

16

36

M

Yes

20/200

20/100

20/100

Absent Present Abnormal Present Abnormal Present

3 4A 4B 5

51 40

M F

Reoperation M 52

0 0 0 0

0

Incomplete CNVM removal Chronic pigmented CNVM

Patient subjectively worse despite improved acuity Patient subjectively much better Prolonged surgical dissection Recurrence lasered -+ 20/60 acuity dropped to 20/200

Fovea ripped

? 2 mos

0 0

Chronic large CNVM

Table 2B. POHS Membrane Disconnections 17

36

F

No

20/30

20/200

20/200

5

18

40

M

Yes

20/60

20/80

20/80

4

19

68

M

Yes

20/100

6/200

6/200

3

20

59

M

No

20/60

20/200

20/200

3

Present Abnormal Present Abnormal Present Abnormal Present Abnormal

Persistent

CNVM left in

0

Could not dissect laser scar, CNVM left in CNVM left in

0

CNVM left in

0

POHS = presumed ocular histoplasmosis syndrome; CNVM = choroidal neovascular membrane; CF = counting fingers; NC = near card; RPE = retinal pigment epithelium.

957

Ophthalmology

Volume 99, Number 6, June 1992

Table 3. Miscellaneous Age (yrs)

Sex

58

M

2

56

F

3

46

M

4 5

42 35

M M

Case No.

Diagnosis Angioid streaks Angioid streaks Idiopathic Idiopathic Serpiginous choroiditis

Preoperative Visual Acuity

Best Postoperative Visual Acuity

Final Visual Acuity

Follow-up (mos)

Yes

20/300

20/300

20/400

16

Absent

No

20/200

20/200

20/200

3

Absent

0

Yes

20/200

20/300

5

RPE patch

1 mo

No No

20/800 NC 20/200

20/100 at 2 mos 20/40 20/20

20/40 20/20

4 4

Present Present

0 0

Previous Laser

Foveal

RPE

CNVM Recurrence

Comments

10 mos Subjectively improved Large RPE patch

Chronic fibrotic CNVM

RPE = retinal pigment epithelium; CNVM = choroidal neovascular membrane; NC = near card.

counting fingers in the left eye had received krypton laser treatment for ajuxtafoveal choroidal neovascular membrane (CNVM) with visual acuity of 20/50 after laser treatment. She presented with a !-month history of blurred vision in the right eye, visual acuity of 20/400, and a subfoveal recurrence (Fig 10). Intraoperatively, gentle nudging of the CNVM with the subretinal pick broke the membrane free but also appeared to dislodge RPE and Bruch's membrane. Forceps removal of the membrane also extracted the contiguous fibrous laser scar (Fig 11 ). Visual acuity returned to 20/70 for 11 months (Fig 12), but at 12 months after surgery, a subfoveal recurrence developed, and visual acuity decreased to 20/100.

Age-related Macular Degeneration Membrane Dis· connections (7 Eyes). With average postoperative follow-up

of 4.4 months (range 3 to 8 months), there was significant improvement in visual acuity in 1 eye, decreased visual acuity in I eye, and visual acuity remaining within 1 line of preoperative levels in 5 eyes (Table !B) (Fig 13). Preoperatively and postoperatively, only I eye had visual acuity better than 20/200. In all cases, foveal RPE was present but progressively lost pigmentation and developed a gray appearance over the ensuing months. Three eyes experienced recurrent neovascularization emanating from the leading or extrafoveal edge of the disconnected membrane 3 to 4 months after surgery.

Case Report Age-related Macular Degeneration Case 24. A 73-

year-old woman presented with visual acuity of20/25 in the left eye and 20/800 by near card acuity in the right, with a 3-month

history of blurring. Thin subretinal blood was present in the macula, overlying a fibrovascular membrane. At surgery, a thin subfoveal neovascular complex, which appeared to lie beneath RPE, was broken free from its choroidal connections. Rather than leave a central RPE defect, the disconnected membrane was repositioned beneath the fovea. Postoperatively, visual acuity initially returned to 20/100 at 2 months and then remained at 20/200 during 6 months of follow-up. Subjectively, the patient reported significant improvement in metamorphopsia and acuity compared with preoperative function. The disconnected membrane appeared to contract and lose pigmentation during 6 months of follow-up.

Age-related Macular Degeneration Retinal Pigment Epithelium Patches (4 eyes). During the first 3 months

after surgery, all 4 eyes experienced either stable or improved acuity. However, with average follow-up of 8.2 months (range, 7 to 11 months), 2 eyes had visual acuities significantly worse than preoperative levels, and the other 2 remained within !line of the preoperative level (Table lC) (Fig 14). This decline in visual acuity over time appeared to correspond with the decrease in size and pigmentation of the RPE patch. One eye developed recurrent neovascularization 3 months after surgery.

Case Report Age-related Macular Degeneration Case 33. A 79year-old man presented with 20/200 acuity and an ill-defined sub-RPE membrane beneath the fovea. During surgery, the membrane was extracted, and an RPE/Bruch's membrane/cho-

Top left, Figure 1. Subfoveal membranes of miscellaneous etiologies. Postoperative final acuity versus preoperative acuity. Closed circles represent eyes with angioid streaks, open circles represent idiopathic membranes, and asterisk represents serpiginous choroiditis. Top right, Figure 2. ARMD removal of choroidal neovascular membranes. Final postoperative versus preoperative visual acuities. tSame patient who underwent repeat vitrectomy for recurrent CNV (Table lA). Second row left, Figure 3. ARMD case 1. Fluorescein angiogram demonstrates subfoveal membrane with 20/200 visual acuity. Second row right, Figure 4. ARMD case 1. Fibrotic neovascular complex with RPE cells (arrow), capillaries with endothelial cells and extensive basement membrane material (hematoxylin-eosin; original magnification, X100). Third row left, Figure 5. ARMD case 1. Fundus appearance 13 months after surgery. Notice absence of RPE. Visual acuity was 20/400. Third row right, Figure 6. ARMD case 16. Preoperative appearance. Visual acuity was 20/80 with subfoveal membrane. Bottom left, Figure 7. ARMD case 16. Preoperative fluorescein angiogram. Late phase. Bottom right, Figure 8. ARMD case 16. Histopathology of extracted membrane. Arrow indicates extracted RPE beneath temporal aspect of membrane. Arrowhead indicates foveal edge of membrane without RPE cells (hematoxylin-eosin; original magnification, Xl00).

958

Thomas et al · Subfoveal Choroidal Neovascularization na~•·•·

..

JOfMO

HfiO

959

Ophthalmology

Volume 99, Number 6, June 1992

riocapillaris patch was dissected from temporal macula and positioned beneath the fovea. Visual acuity remained 20/200 for 2 months, then declined to 20/800 by near card at 7 months (Fig 15). No recurrent neovascularization was seen, but the tissue patch contracted and lost pigmentation.

Presumed Ocular Histoplasmosis Syndrome ZA. Presumed Ocular Histoplasmosis Syndrome Membrane Removals (16 eyes). With limited average fol-

low-up of 4.8 months (range, 1 to 13 months), final visual acuity significantly improved in 6 eyes, declined in l, and remained unchanged in 9 (Table 2A) (Fig 16). Four eyes achieved 20/70 acuity or better. Six of 16 eyes (37%) developed either persistent or recurrent neovascularization, on average 4 months after surgery. A seventh eye (POHS case 14) developed suspicious hyperfluorescence at 2 months, which longer follow-up may confirm as recurrence. Final visual acuity was improved compared with preoperative acuity in only one of these eyes with postoperative membrane recurrence. In many cases of POHS, the fibrovascular membranes appeared to involve underlying RPE and Bruch's membrane; surgical extraction of subfoveal pigment epithelium occurred in at least four eyes. In 12 eyes, pigment epithelium was believed to be present although disturbed after surgery.

Case Reports Presumed Ocular Histoplasmosis Syndrome Case

14. A 39-year-old woman with POHS had undergone 2 kryp-

ton laser treatments for juxtafoveal neovascularization elsewhere 2 months before presentation. Visual acuity in the affected eye was 20/200, and recurrent neovascularization on the nasal (foveal) side of the laser scar was apparent with subfoveal extension. At surgery, the recurrent membrane appeared to peel off underlying RPE. However, it remained tethered to the previous laser scar. Subretinal forceps were used to grasp this residual stalk of tissue and extract the scar and membrane. Postoperatively, visual acuity improved to 20/25 at 1 month and RPE appeared to be present but abnormal beneath the nasal half of the fovea. At 2 months, visual acuity had declined to 20/50 and angiography suggested early subfoveal recurrence.

Presumed Ocular Histoplasmosis Syndrome Case

6. A 51-year-old man developed a subfoveal fibrovascular

membrane 8 months before presentation with extensive subretinal exudation, lipid accumulation, and blood. Visual acuity was counting fingers at 2 feet (Fig 17). At surgery, subretinal forceps were used to grasp the narrow neck of the fibrotic mass and extract the complex. Results of histopathology showed a spherical structure with extensive vascularity and basement membranelike matrix (Fig 18). Postoperatively, foveal RPE appeared to be absent, but the detachment resolved, visual acuity improved to 20/400, and the patient experienced significant subjective improvement (Fig 19).

Presumed Ocular Histoplasmosis Syndrome Case 16. A 36-year-old man developed subfoveal recurrent neo-

vascularization after macular photocoagulation and visual acuity decreased to 20/200. Sixteen months later, he presented with visual acuity of 20/200 and a shallow, exudative, neurosensory retinal detachment overlying a large fibrotic scar (Fig 20 and 21). During surgery, the fibrotic plaque peeled off underlying RPE. Postoperatively, by 1 month he had significant subjective improvement in metamorphopsia and size of his central scotoma; objectively, visual acuity improved to 20/100 (Fig 22).

ZB. Presumed Ocular Histoplasmosis Syndrome Membrane Disconnections (4 Eyes). The first three cases

listed in Table 2B were eyes in which extraction of the membrane was planned but at surgery was found to not be possible without removing foveal RPE; therefore, disconnection of the complex was performed instead. In case 20, clinical examination and angiography clearly demonstrated a sub-RPE membrane centered in the fovea. Rather than produce an RPE defect, the pick was passed behind the RPE and membrane in the central macula. All four patients experienced a significant decline in visual acuity postoperatively, with average postoperative follow-up of 3.8 months (Fig 16).

Case Report Presumed Ocular Histoplasmosis Syndrome Case

18. A 40-year-old man presented with visual acuity of 20/60

in the right eye and a discrete subfoveal recurrent membrane adjacent to a deeply pigmented photocoagulation scar (Figs 23

Top left, Figure 9. ARMD case 16. Appearance 2 months after surgery. Visual acuity was 20/20. Arrow indicates RPE defect, arrowhead indicates mild foveal pigment disturbance, and hollow arrow indicates retinotomy. Top right, Figure 10. ARMD case 7. Fluorescein angiogram demonstrates recurrent subfoveal membrane. Visual acuity was 20/400. Second row left, Figure 11. ARMD case 7. Histopathology of extracted CNVM. Arrow indicates fibrous laser scar connected to recurrent membrane. (Point of connection to the left of this magnified view.) Note absence of neurosensory retinal elements overlying avascular laser scar. Arrowhead indicates recurrent fibrovascular membrane adherent to RPE and underlying Bruch's membrane (hematoxylin-eosin; original magnification, XlOO). Second row right, Figure 12. ARMD case 7. One month postoperative angiogram. Note absence of RPE and choriocapillaris in area of extracted recurrence. Third row left, Figure 13. ARMD disconnection of choroidal neovascular membranes. Final postoperative versus preoperative visual acuities (Table lB). Third row right, Figure 14. ARMD-RPE patches. Final postoperative versus preoperative visual acuities (Table 1C). Bottom left, Figure 15. ARMD case 33. Three month postoperative appearance of RPE/Bruch's membrane/choriocapUlaris patch beneath fovea. Visual acuity was 20/200. Visual acuity subsequently declined to 20/800 by near card at 7 months. No recurrent neovascularization was seen, but the tissue patch contracted and lost pigmentation. Bottom right, Figure 16. POHS. Removal and disconnection of choroidal neovascular membranes. Final postoperative versus preoperative visual acuities. Solid circles represent membrane removal cases, open squares indicate cases in which the membrane was disconnected. t and t indicate two patients who underwent repeat vitrectomy for recurrent CNV (Tables 2A and 2B).

960

Thomas et al · Subfoveal Choroidal Neovascularization

...... .....

......... -

"!.c-

":.-

"::-

"~

J•l -

"'" M/M

"'"'-

/

/

./

/

/

,.,,. M/M M/M M/M

..

,...

/

961

Ophthalmology

Volume 99, Number 6, June 1992

and 24 ). RPE pigment migration into neurosensory retina was present over the scar. During surgery, the recurrent membrane peeled off underlying RPE easily but it remained firmly connected to the laser scar. Multiple attempts were made with the subretinal pick to break the adhesions between the laser scar and overlying neurosensory retina, but they were unsuccessful. Because extraction of the subfoveal membrane would have torn neurosensory retina, it was deemed preferable to disconnect the fibrous laser scar from underlying choroid. The pick passed easily behind the old scar. Postoperatively, metamorphopsia persisted and visual acuity was 20/80 at 4 months. The area of chorioretinal scarring was larger than that seen preoperatively (Fig 25). Results of angiography showed staining throughout the scar without focal leakage from the subfoveal component.

Subfoveal Membranes of Other Etiologies Membranes in the two eyes with angioid streaks were inseparable from underlying RPE, and, thus, RPE defects were presumably created at surgery (Table 3) (Fig 1). Visual acuity was limited to 20/400 and 20/200. In case 3, a large peripapillary membrane, previously lasered, grew beneath the fovea. The patient declined intervention for 4 months; visual acuity had decreased to 20/200, and the membrane had significantly enlarged. At surgery, a large apron of adjacent RPE came out during the membrane extraction. This was cut free inside the vitreous cavity and repositioned under the fovea. Visual acuity stabilized at 20/300 despite the apparent shrinking and depigmentation of the patch. The second eye with an idiopathic membrane and the eye with serpiginous choroiditis experienced dramatic visual return. The idiopathic case improved from 20/800 by near card to 20/40, and the eye with serpiginous improved from 20/200 to 20/20.

Case Reports Miscellaneous Case 4. A 42-year-old man presented with a 2-week history of visual loss, a subfoveal membrane (idiopathic), thin subretinal blood, and visual acuity of 20/800 by near card (Figs 26 and 27). The membrane appeared to lie an-

terior to RPE on stereoscopic fundus examination. At surgery, the central fibrovascular stalk was identified with the pick, and the surrounding edges of membrane were lifted gently off underlying RPE. The central stalk was grasped with forceps and extracted. By 4 months postoperatively, visual acuity had improved to 20/40. Although a rim of blood adjacent to the old scar was seen at 4 months, no recurrent neovascularization could be identified angiographically (Fig 28). Miscellaneous Case 5. A 35-year-old man developed an atrophic scar at the site of previous inflammation from serpiginous choroiditis adjacent to the right fovea. Subsequently, choroidal neovascularization arose beneath the center of the fovea. During 2 years' observation by a retinal specialist, acuity varied between 20/200 and 20/500 (Fig 29). On presentation, visual acuity was 20/200 eccentrically, and a shallow neurosensory retinal detachment was seen overlying a large fibrotic scar (Figs 30 and 31 ). During surgery, the fibrovascular membrane was found to be adherent to both underlying RPE and overlying neurosensory retina. Forceful manipulation with the subretinal pick dislodged the complex in toto from surrounding structures. As the membrane was pulled from the subretinal space with forceps, the retinotomy enlarged slightly. Postoperatively, the preexisting serpiginous scar was evident, as was the lasered retinotomy, but RPE elsewhere in the macula was preserved and subretinal fluid resorbed (Fig 32). Visual acuity returned to 20/ 40 at 2 months and was 20/20 at 4 months.

Foveal Retinal Pigment Epithelium Removal Of 26 eyes with ARMD in which subfoveal vessels were removed, 21 appeared to lose subfoveal RPE at the time of extraction (81% ). Of 16 POHS membrane removals, only 4 (25%) appeared to have subfoveal RPE defects, although the RPE was abnormal in appearance in most of the other cases. Three of five of the miscellaneous cases appeared to lose foveal RPE. When RPE appeared to be present, good vision was achieved in some cases. The 2 eyes with 20/20 acuity (ARMD case 16 and miscellaneous case 5 serpiginous), as well as the eye with 20/40 visual acuity (miscellaneous case 4) all had foveal RPE after surgery. The 3 eyes with POHS that achieved visual acuity better than 20/80 had foveal RPE, while the apparent absence of RPE was associated with visual acuity worse than or equal to 20/100

Top left, Figure 17. POHS case 6. Chronic exudative posterior pole detachment secondary to subfoveal fibrotic membrane. Visual acuity was counting fingers at 2 feet. Arrow indicates subretinal fibrotic scar. Top right, Figure 18. POHS case 6. Histopathology of extracted fibrotic mass. Arrow indicates narrow subfoveal neck connecting to choroid. Extensive basement membrane material, capillaries, and RPE cells present on surface (hematoxylin-eosin; original magnification, X40.) Second row left, Figure 19. POHS case 6. Appearance 1 month after surgery, with resolution of detachment. Visual acuity was 20/400. Disc (not seen) is to the left. Because of flattening of the neurosensory retinal detachment and removal of the thick scar, the vascular landmarks appear quite different in this postoperative photograph. Arrow indicates absent foveal RPE at the site of choroidal ingrowth. Arrowhead indicates pigmented retinotomy scar temporal in macula. Second row right, Figure 20. POHS case 16. Chronic fibrotic membrane with exudative detachment. Visual acuity was 20/200. Third row left, Figure 21. POHS case 16. Angiogram demonstrates well-defined membrane. Third row right, Figure 22. POHS case 16. One month postoperative appearance with preserved RPE, resolved exudative detachment, and less lipid. Arrow indicates retinotomy scar, and arrowhead indicates prior photocoagulation scar. Bottom left, Figure 23. POHS case 18. Densely pigmented photocoagulation scar with discrete subfoveal recurrence. Bottom right, Figure 24. POHS case 18. Angiogram of recurrent membrane.

962

Thomas et al · Subfoveal Choroidal Neovascularization

963

Ophthalmology

Volume 99, Number 6, June 1992

in all categories. Foveal RPE was presumably present postoperatively in many eyes that did not have good vision. Three of the 4 eyes with ARMD and foveal RPE had acuities of 20/200 to 20/400. In 8 of 16 POHS eyes with RPE, visual acuity was 20/200 or worse.

Previous Laser Scars Twenty-two of 58 eyes had scars from previous laser photocoagulation. Of these, five membranes and scars were disconnected (three eyes with ARMD had intentional disconnection and in two eyes with POHS it was impossible to extract the membrane; therefore, disconnection was performed instead). Therefore, 17 eyes had laser scars associated with membrane removal. In all seven ARMD eyes, the laser scar was extracted with the membrane. In seven of eight POHS eyes, the laser scar was extracted with the membrane. Two of the miscellaneous eyes had extraction of laser scars with the membrane.

Statistical Analysis Multivariate analysis was applied to the data on postoperative visual acuity using the following variables: age, sex, previous laser photocoagulation, preoperative visual acuity, best postoperative visual acuity, presence offoveal RPE, and CNVM recurrence. Preoperative visual acuity (P = 0.03) and presence of foveal RPE (P = 0.07) were positively correlated with postoperative acuity. Younger age also was correlated with better visual outcome for patients with ARMD membrane disconnection (P = 0.07). Because of the small number of patients in each group, no other statistically significant correlations were found.

Complications (58 Cases) Intraoperative A small amount of hemorrhage under the macula occurred in 15 cases (26%) at the moment of membrane

extraction. These hemorrhages were self-limited, did not require removal, did not interfere with intraoperative photocoagulation of the retinotomy, and in most cases had resolved by the first morning after surgery. Two patients experienced significant hemorrhages with thick blood beneath the fovea. In both, the clot was removed during the primary surgery, but the retinotomy enlarged. Retinal tears occurred in four eyes, two in the periphery related to sclerotomies (treated with cryopexy and/or scleral buckles at the time of the first surgery) and two in the macula on the edge of previous photocoagulation scars. One of these posterior tears occurred as balanced salt solution was slowly injected into the subretinal space; the juxtafoveal laser scar pulled off and the fovea tore (ARMD case 12; final visual acuity, 20/200). Green 30 has documented that neurosensory retina in photocoagulation scars may be reduced to a "thin, fibrogliotic strand." It is not surprising that even a gentle infusion of fluid could tear such attenuated tissue. The other tear occurred during forceps extraction of a recurrent POHS membrane. The previous laser scar demonstrated hyperpigmentation and remained adherent to neurosensory retina (POHS case 13).

Postoperative Two rhegmatogenous retinal detachments developed during the early postoperative period. In one, a small inferior hole was probably created during the stripping of the posterior hyaloid. In the second, the patient did not maintain face down positioning after surgery and probably detached from his retinotomy. Both of these detachments were repaired with scleral buckles, repeat gas-fluid exchanges, and laser. The follow-up in this report is too brief to comment on the incidence of cataract. Presumably all phakic eyes will develop lens opacities sooner than if vitrectomy surgery had not been performed. Four eyes (7%) developed preretinal membranes (macular pucker) with only mild distortion of neurosensory retina. Although not encountered in this group of patients, one must remember the risk of serious complications such as anes-

Top left, Figure 25. POHS case 18. Four-month postoperative appearance. Chorioretinal scar is larger than seen preoperatively. Visual acuity was 20/80. Top right, Figure 26. Miscellaneous case 4 (idiopathic). Subfoveal membrane with hemorrhage and acuity 20/800 by near card. Second row left, Figure 27. Miscellaneous case 4 (idiopathic). Central, well-defined membrane. Second row right, Figure 28. Miscellaneous case 4 (idiopathic). Postoperative appearance at 4 months with mild RPE metaplasia at retinotomy site and choroidal ingrowth site. Visual acuity was 20/40. Third row left, Figure 29. Miscellaneous case 5 (serpiginous). Subfoveal membrane arising from macular scar. Visual acuity was 20/200. Third row right, Figure 30. Miscellaneous case 5 (serpiginous). Preoperative appearance, 1 year after Figure 29. Visual acuity was 20/200. Bottom left, Figure 31. Miscellaneous case 5 (serpiginous). Fluorescein angiogram with well-defined fibrotic membrane and faint halo indicating extent of chronic neurosensory detachment (arrows). Bottom right, Figure 32. Miscellaneous case 5 (serpiginous). Appearance one month following surgery. Arrow indicates old serpiginous scar. Arrowhead indicates lasered retinotomy scar. Retina was flat and visual acuity was 20/40 without evidence of recurrent neovascularization. By 2 months after surgery, visual acuity had improved to 20/20.

964

Thomas et al · Subfoveal Choroidal Neovascularization

965

Ophthalmology

Volume 99, Number 6, June 1992

thesia problems, adverse systemic effects of surgery, and endophthalmitis.

Discussion Based on the experience of these first 58 cases, several observations can be made. 1. Surgical removal of choroidal neovascular membranes through a small retinotomy is technically feasible. As facilitated with new instrumentation, 29 the fibrovascular complex can be dislodged in the subretinal space and extracted, usually with minimal hemorrhage and with minimal enlargement of the retinotomy. The cohesiveness of the tissue, its tensile strength, and the paucity of capillaries facilitate such surgical manipulation. 2. In the majority of cases, extraction ofsubfoveal vessels produces an apparent defect in RPE/Bruch's membrane/choriocapillaris. This fact is presumably related to the intrinsic growth patterns of choroidal neovascularization. In ARMD, the fibrovascular membrane may be found histologically within Bruch's membrane, beneath RPE, and beneath subneurosensory retina. 2•30 Thus, during surgery, membrane removal usually entails extraction of all these tissues. In idiopathic and postinflammatory maculopathies, the choroidal neovascularization may have a solitary ingrowth site through a focal abnormality in Bruch's membrane. Thus, the neovascular membrane may grow anteriorly into the subneurosensory retinal space or may have a pattern of more diffuse growth and involvement on both sides of the RPE. 30 This varied pattern in nonARMD cases may contribute in part to the varied response to surgery. In some cases, a membrane anterior to RPE can be removed with minimal disruption of RPE/Bruch's membrane/choriocapillaris, while, in other cases, these underlying tissues are enmeshed in the membrane and are removed simultaneously. 3. Foveal RPE and choriocapillaris may be necessary for good central visual function since all three eyes with excellent vision appeared to have these tissues intact. Conversely, no eyes without foveal RPE had visual acuity better than 20/100. Depending on preoperative characteristics, some patients may have significant improvement in symptoms even if central RPE is disturbed or absent after surgery. POHS case 6 experienced resolution of a chronic exudative retinal detachment after removal of the membrane, which unfortunately involved foveal RPE. Although visual acuity measured only 20/400, the patient was subjectively much better. Similarly, ARMD case 14 underwent removal of foveal RPE with a large neovascular complex. Postoperative visual acuity remained 20/200, but the exudative RD resolved and the patient experienced significant subjective improvement.

966

4. Poor vision after surgery may be due to a variety of causes. Preoperative factors that might limit visual success include: pre-existent RPE and/or photoreceptor damage, whether from the sequelae of neovascularization (hemorrhage, lipid, fluid, or scar growth), the effects of underlying macular disease (such as postinflammatory scars or the RPE dysfunction of ARMD), or the effects of previous laser photocoagulation. Most patients presented with poor vision, and it was not possible to ascertain if retinal dysfunction was already irreversible. Intraoperative factors that could limit subsequent vision include: photoreceptor and/or RPE damage from mechanical instrument trauma, damage from the subretinal infusion of fluid, damage from intense endoillumination, 31 and possible removal of the RPE. Postoperative factors affecting visual outcome would include new membrane recurrence and the development of complications such as retinal detachment. Only randomization with a control group and a prospective study could assess the relative contribution of each factor. 5. Disconnecting fibrovascular membranes and placement of RPE patches fail to improve significantly visual outcome compared with membrane removal alone. Once RPE has been disconnected from underlying choroid, it appears to lose function, as evidenced by contraction of the tissue or patch, loss of pigmentation, the development of a gray appearance, and reduction in visual acuity. 6. Most pre-existing laser photocoagulation scars are extracted with the removal of subfoveal vessels. However, hyperpigmentation of scars and pigment migration into neurosensory retina are signs of firm chorioretinal adhesion and may prevent surgical removal (e.g., POHS case 18). 7. Recurrent choroidal neovascularization is a frequent complication of this surgical procedure and carries a worse visual prognosis than if the macula remains free of recurrence. Recurrences may be extrafoveal or juxtafoveal and thus amendable to standard laser therapy. Several patients experienced significant visual improvement for a period of months after surgery until recurrent neovascularization and/or photocoagulation for the recurrent vessels (e.g., ARMD cases 3, 6, and 7, and POHS cases 1, 9, and 14). Two of the three patients who underwent repeat vitrectomy for recurrent neovascularization experienced increased vision, at least for a period of time (ARMD case 3, POHS case 1). It is unclear whether recurrences develop because of the underlying disease process itself or because of the surgery. Rates of recurrence in this group of patients (30% for ARMD and 37% for POHS) may end up higher than MPS figures with longer-term follow-up. Obviously, the fact that one third of patients experienced recurrence with only 8 months follow-up in ARMD and 5 months of follow-up in POHS suggests that 12-month and 24-month cumulative rates may be higher. Presumably, this will lead to worse visual results with longer follow-up.

Thomas et al · Subfoveal Choroidal Neovascularization Currently, we are assessing the possible value of systemic interferon alpha 2A in blocking or limiting recurrent neovascularization. As recently reported by Fung, 32 some patients have shown regression of subfoveal choroidal neovascularization when treated with interferon at a dose of 3 million units per meters squared body surface area every other day for 8 weeks. If an effective antiangiogenic drug can be identified, then pharmacologic intervention may carry less risk than invasive vitrectomy surgery. It may be that some eyes would benefit from surgical removal of fibrovascular scars with subsequent administration of an antiangiogenic drug to block the development of recurrent neovascularization. 8. As with any new surgery, improvements in instrumentation and techniques may improve outcome. The principal limitations of this technique probably stem from inherent characteristics of the underlying disease and the growth pattern of the fibrovascular membrane. However, instruments designed specifically for use in the subretinal space through a small retinotomy may allow better removal of membranes with less destruction of normal tissue. We reported the use of a 20-gauge endolaser probe in the subretinal space to cauterize a bleeding site on Bruch's membrane after extraction of a submacular hematoma. 33 Subsequently, we developed a 25-gauge angled endolaser probe for use in the subretinal space (unpublished data; presented at the 24th Annual Meeting of The Retina Society, Quebec, 1991 ). Subretinal laser photocoagulation of certain subfoveal membranes is currently under evaluation. This device may prove to be a useful adjunct in subretinal surgery. Our results show that some eyes have experienced a dramatic return of central visual function that would have been unlikely with either observation or currently available photocoagulation techniques. Although the number of patients with excellent central vision after surgery is small, those eyes do seem to have some findings in common. It is our clinical impression that these favorable findings include clearly demarcated borders on fundus examination with discernible edges of the membrane discrete from underlying and surrounding RPE, the absence ofhyperpigmentation and intraretinal pigment migration near the fovea, and angiographic evidence of a well-defined membrane (without surrounding late hyperfluorescence at the level of the RPE indicative of sub-RPE or occult neovascularization). Some of these eyes can undergo surgical extraction of the neovascular membrane and preserve functional RPE and functional neurosensory retina. We do not yet have adequate experience to predict precisely which eyes will have this favorable response to surgery. With present techniques, surgery in most cases of subfoveal neovascularization secondary to ARMD will not result in good central visual function. Given our present understanding, we do not advise application of this technique in most cases of subfoveal neovascularization secondary to ARMD. Lesser goals such as resolution of

exudative neurosensory retinal detachment and thus limitation of scotoma size may be achieved, but it is possible that slit-lamp photocoagulation can achieve the same goals with less invasive therapy. Certain ARMD cases may be better served with surgery than with observation or laser, but refined case selection is needed. If surgery is performed, there is a significant risk of recurrent neovascularization. Some cases of subfoveal membranes secondary to POHS and miscellaneous etiologies appear to fare better with surgery than would have been generally expected with observation or foveal photocoagulation. Longer-term follow-up and experience with more patients will be required before precise surgical indications can be offered. The problem of recurrent neovascularization following successful surgery is of major significance and warrants careful follow-up. Surgical management of subfoveal neovascularization holds promise for improving visual function in certain eyes for which previously few therapeutic options existed. We are at present gaining experience with the technique, extending patient follow-up, improving instrumentation, and refining patient selection to identify groups of patients for whom a randomized, prospective clinical trial would be appropriate. Alternative or adjunctive approaches to subfoveal neovascularization including pharmacologic agents and subretinal endolaser photocoagulation merit further evaluation. Acknowledgments. The authors thank FeiFei Wei, PhD, for statistical analysis.

References 1. Green WR, Wilson DJ. Choroidal neovascularization. Ophthalmology 1986;93:1169-76. 2. Gass JDM. Pathogenesis of disciform detachment of the neuroepithelium. III. Senile disciform macular degeneration. Am J Ophthalmol 1967;63:617-44. 3. Bressler SB, Bressler NM, Fine SL, et al. Natural course of choroidal neovascular membranes within the foveal avascular zone in senile macular degeneration. Am J Ophthalmol 1982;93: 157-63. 4. Olk RJ, Burgess DB, McCormick PA. Subfoveal and juxtafoveal subretinal neovascularization in the presumed ocular histoplasmosis syndrome: visual prognosis. Ophthalmology 1984;91: 1592-602. 5. Vander JF, Morgan CM, Schatz H. Growth rate ofsubretinal neovascularization in age-related macular degeneration. Ophthalmology 1989;96: 1422-9. 6. Macular Photocoagulation Study Group. Argon laser photocoagulation for idiopathic neovascularization. Results of a randomized clinical trial. Arch Ophthalmol 1983;101: 1358-61. 7. Macular Photocoagulation Study Group. Argon laser photocoagulation for ocular histoplasmosis. Results of a randomized clinical trial. Arch Ophthalmol 1983; 101: 134 757. 8. Macular Photocoagulation Study Group. Argon laser photocoagulation for senile macular degeneration. Results of a randomized clinical trial. Arch Ophthalmol 1982;100:912-8. 9. Macular Photocoagulation Study Group. Krypton laser photocoagulation for neovascular lesions of age-related

967

Ophthalmology

10.

II.

12.

13.

14. 15. 16.

17.

18.

19.

20. 21.

Volume 99, Number 6, June 1992

macular degeneration. Results of a randomized clinical trial. Arch Ophthalmol 1990; I 08:816-24. Macular Photocoagulation Study Group. Krypton laser photocoagulation for idiopathic neovascular lesions. Results of a randomized clinical trial. Arch Ophthalmol 1990; 108: 832-7. Macular Photocoagulation Study Group. Krypton laser photocoagulation for neovascular lesions of ocular histoplasmosis. Results of a randomized clinical trial. Arch Ophthalmol 1987;105: 1499-507. Macular Photocoagulation Study Group. Laser photocoagulation of subfoveal neovascular lesions in age-related macular degeneration. Results of a randomized clinical trial. Arch Ophthalmol 1991; I 09:1220-31. Macular Photocoagulation Study Group. Laser photocoagulation of subfoveal recurrent neovascular lesions in agerelated macular degeneration. Results of a randomized clinical trial. Arch Ophthalmol 1991; I 09: 1232-41. Boldrey EE. Foveal ablation for subfoveal choroidal neovascularization. Ophthalmology 1989;96: 1430-6. Schachat AP. Management of subfoveal choroidal neovascularization [editorial]. Arch Ophthalmol 1991; 109:1217-8. Macular Photocoagulation Study Group. Recurrent choroidal neovascularization after argon laser photocoagulation for neovascular maculopathy. Arch Ophthalmol 1986; I 04: 503-12. Macular Photocoagulation Study Group. Persistent and recurrent neovascularization after krypton laser photocoagulation for neovascular lesions of age-related macular degeneration. Arch Ophthalmol 1990; I 08:825-31. Macular Photocoagulation Study Group. Persistent andrecurrent neovascularization after krypton laser photocoagulation for neovascular lesions of ocular histoplasmosis. Arch Ophthalmol 1989;107:344-52. Macular Photocoagulation Study Group. Manual of Procedures(rev.Oct.l, 1989,selectedchaps.rev.Jan.l, 1991). Available from: National Technical Information Service (Accession No. PB91-159368-XAB). Bennett SR, Folk JC, Blodi CF, Klugman M. Factors prognostic of visual outcome in patients with subretinal hemorrhage. Am J Ophthalmol 1990; I 09:33-7. deJuan E Jr, Machemer R. Vitreous surgery for hemorrhagic and fibrous complications of age-related macular degeneration. Am J Ophthalmol 1989;105:25-9.

968

22. Blinder KJ, Peyman GA, Paris CL, Gremillion CM Jr. Submacular scar excision in age-related macular degeneration. Int Ophthalmol 1991; 15:215-22. 23. Peyman GA, Blinder KJ, Paris CL, et al. A technique for retinal pigment epithelium transplantation for age-related macular degeneration secondary to extensive subfoveal scarring. Ophthalmic Surg 1991 ;22: 102-8. 24. Thomas MA, Kaplan HJ. Surgical removal of subfoveal neovascularization in the presumed ocular histoplasmosis syndrome. Am J Ophthalmol 1991; Ill: 1-7. 25. Macular Photocoagulation Study Group. Subfoveal neovascular lesions in age-related macular degeneration. Guidelines for evaluation and treatment in the Macular Photocoagulation Study. Arch Ophthalmol 1991;109:124257. 26. Grizzard WS, Allarakhia L. New silicone tipped cannulas for subretinal fluid drainage. Br J Ophthalmol 1989;73:838-9. 27. Han DP, Abrams GW, Aaberg TM. Surgical excision of the attached posterior hyaloid. Arch Ophthalmol1988; I 06:9981000. 28. Mein CE, Flynn HW Jr. Recognition and removal of the posterior cortical vitreous during vitreoretinal surgery for impending macular hole. Am J Ophthalmol 1991; Ill :61113. 29. Thomas MA, Lee CM, Pesin SR, Lowe MA. New instruments for submacular surgery. Am J Ophthalmol 1991; 112: 733-4. 30. Green WR. Clinicopathologic studies of treated choroidal neovascular membranes. A review and report of two cases. Retina 1991;11:328-56. 31. Zilis JD, Machemer R. Light damage in detached retina. Am J Ophthalmo11991;111:47-50. 32. Fung WE. Interferon alpha 2a for treatment of age-related macular degeneration [letter]. Am J Ophthalmol 1991; 112: 349-50. 33. Thomas MA, Halperin LS. Subretinal endolaser treatment of a choroidal bleeding site [letter]. Am J Ophthalmol 1990; 109:742-4.

Discussion of this and the following article appears on page 975.