Abstract
purpose. To develop a novel technique, fine needle diathermy (FND), for the
occlusion of corneal vessels and to evaluate its safety and efficacy in
a series of patients.
methods. Fourteen patients were treated with FND to occlude corneal vessels.
Patients were categorized into four groups: group 1
(n = 4), high risk patients with stromal
vascularization before keratoplasty; group 2 (n =
2), patients with progressive lipid keratopathy; group 3
(n = 4), post keratoplasty patients with active
rejection episodes associated with vessels; and group 4
(n = 4), patients with disciform vascularized scars
with recurrent inflammation. The success of the treatment in terms of
vessel occlusion and the clinical outcome were monitored.
results. All patients in group 1 had successful corneal transplantation, and the
grafts remained clear without graft rejection. Patients in group 2 with
lipid keratopathy had 100% obliteration of vessels with stabilization
of corneal scar. All four patients in group 3 had complete regression
of vessels with reversal of graft rejection. Patients with vascularized
disciform scar had resolution of the inflammation without recurrence.
Average follow-up was 10.3 months (minimum, 6 months; maximum, 24
months). No serious complications were observed with FND.
conclusions. FND is a useful and inexpensive technique that can serve as an adjunct
or alternative to laser occlusion for the treatment of established
corneal vessels. It is fairly safe and effective, although
complications such as intrastromal bleeding and crystalline deposits
can occur and at times it may have to be repeated once or twice to
achieve the desired result.
The avascularity of the cornea is one of its unique features.
Absence of vessels helps to maintain the cornea in a transparent state
and also confers a degree of immune privilege to the
cornea.
1 2 However, blood vessels are important for the
host to mount a healing response against injury and infection. Corneal
neovascularization occurs as a sequel to corneal insult resulting from
infectious, allergic, toxic, anoxic, and immune causes whereupon it
serves to facilitate the healing process or acts as a warning sign of
corneal distress.
3 4 Once established, these vessels help
to transport humoral and cellular elements of immunologic defense and“
raw material” required for repair and regeneration. They also help
to carry administered antibiotics and other drugs to the site of
infection and at the same time eliminate toxic substances.
The disadvantage of the corneal neovascular response is that once the
healing process is completed, the vessels often persist with
circulating blood. This may interfere with corneal transparency by
leakage of lipids or by recurrent inflammation. A sequel of corneal
vascularization is the establishment of lymphatics, which are normally
absent in the cornea. Lymphatics augment the afferent arc of the immune
response, favoring sensitization to corneal and other antigens. Corneal
vascularization also disrupts the “immune privilege” status of the
cornea and jeopardizes the survival of a corneal graft, which is often
required in such situations to restore vision. It is an established and
recognized risk factor for corneal graft rejection and
failure.
5 6
Various modalities of treatment have been used to directly or
indirectly occlude corneal vessels, including steroids, radiation,
cystine, cryotherapy, sulfuric acid, dextran, and conjunctival
recession.
6 7 8 9 The argon laser
10 11 12 13 14 15 and the
577-nm yellow dye lasers
16 17 have also been used to
obliterate corneal vascularization, treating vascularization in lipid
keratopathy and graft rejection. Pregraft treatment of corneal
vascularization has been found to improve the chances of graft survival
after keratoplasty.
18 Current evidence suggests that the
yellow dye laser (577 nm) is the most effective therapeutic modality to
treat corneal vessels.
16 17 However, the lack of
availability and the expense of this equipment in most centers makes
the treatment inaccessible to most ophthalmologists.
We have developed an alternative, simple, and inexpensive method of
occluding corneal vessels called fine needle diathermy (FND). Our main
aim was to assess and report the efficacy and safety of this method of
vessel occlusion. Whether the objectives of vessel occlusion (e.g.,
clearance of lipid keratopathy or prolonged graft survival) were
achieved or not will be described to some extent and constitute the
secondary aim of this report.
Fourteen patients with corneal vascularization were selected and
prospectively followed at the Queens Medical Center, University
Hospital, Nottingham, from June 1995 to April 1998. Informed consent
was obtained from all patients before their inclusion in the study. The
research followed the tenets of the Declaration of Helsinki, and the
protocol was approved by the local Ethics Committee of the Queens
Medical Center.
Details were taken on the cause and duration of corneal vascularization
and whether any prior treatment was given. In each patient, the extent
of corneal vascularization was recorded with respect to the number of
quadrants involved, the depth of vessels, and whether they were active
or quiescent. History regarding previous treatment of corneal
vascularization with argon laser, systemic steroids, and
immunosuppression was also noted.
Pre- and posttreatment anterior segment color photographs were taken to
compare and study the effectiveness of the procedure.
Measurement of the extent of corneal vascularization was performed
using a semiquantitative method by counting the number of “red
lines” (blood-filled vessels both superficial and deep in the cornea)
in each quadrant. The result was expressed as the total number of red
lines per quadrant of corneal vascularization.
Amethocaine 1% eye drops were used to induce topical anesthesia
(in children general anesthesia was used). Using an operating
microscope set at a low intensity of illumination (to reduce
blepharospasm and reflex Bell’s phenomenon), a wire lid speculum was
inserted to keep the eye open. In more light sensitive individuals, a
green filter (TG 475 nm wavelength) was introduced in the light path.
Using the microscope, the depth of vessels was assessed and the number
of vessels in each quadrant to be cauterized was noted.
A stainless steel 3/8 circle side cutting, single-armed needle attached
to a 10–0 monofilament black nylon suture was used with a
microsurgical needle holder (dimensions: 0.15 mm cross-sectional
diameter, 6.19 mm overall length; catalog No. 8065-208001; Alcon
Surgical, Hemel Hempstead, UK). The needle was inserted close to the
limbus, parallel to and at same depth as the blood vessel(s) to be
occluded. With relatively larger vessels it was possible to insert the
tip of the needle into the lumen of the blood vessel(s). This was not
normally associated with bleeding unless the needle was inadvertently
withdrawn before application of the diathermy probe. A unipolar
diathermy unit (Valley Laboratory UK, Pfizer Hospital Products) was set
to its lowest setting (0.5–1 mA). (Any unipolar diathermy unit with
the capability of low power setting could be used.) An appropriate
electrode was strapped around the foot of the patient and connected to
the equipment. In the coagulating mode, the diathermy probe was brought
into contact with the corneal needle, and contact was maintained until
mild blanching of the corneal stroma occurred (usually a second or
less;
Fig. 1 ). Each feeder vessel was treated individually. For vessels spread along
the graft–host junction and for very deep vessels arising from an iris
adhesion, the needle was passed in a circumferential manner. Most of
the vessels were treated in one session, but occasionally it was
necessary to repeat the procedure at a later date to occlude secondary
(collateral) vessels, which developed after the first session. The
objective was always to treat the afferent vessels before occluding the
efferents. Where the afferent and efferent vessels were close together,
it was possible to treat both of them simultaneously by a single pass
of the needle.
After the procedure, patients were treated with chloramphenicol 0.5%
and dexamethasone 0.1% eye drops for 1 week. Patients with a history
of herpes simplex keratitis were given additional prophylactic topical
3% acyclovir eye ointment.
Patients were followed-up at 2 weeks posttreatment and then every 2
months for 6 months. At each follow-up visit, patency and
recanalization of vessels, visual acuity, intraocular pressure, and any
other complications were noted. Patency of vessels was assessed using
slit-lamp biomicroscope examination by observing the flow of red blood
cells through corneal vessels.
All four patients in group 1 underwent successful PK. Three had
post PK treatment with oral FK506, an immunosuppressant agent
(Tacrolimus, Prograf, Fujisawa Ltd. Japan), a macrolide antibiotic with
potent immunosuppressive activity, isolated from the soil fungus Streptomyces tsukubaensis). Not a single episode of
rejection was observed in any of these patients until the last
follow-up (minimum 9 months post PK).
All vessels in patients of group 2 were successfully closed immediately
and remained shut throughout the period of follow-up. The progression
of lipid keratopathy was arrested, but deposited lipids showed only
marginal clearance at the time of last follow-up visit (24 months). In
the four patients in group 3, with rejection reactions persisting for 1
to 2 weeks, unresponsive to topical and subconjunctival steroids and to
attempted closure with argon laser (3 patients), the rejection resolved
within 2 to 3 days after occlusion of vessels by FND. Steroid drops
were continued after FND occlusion of the vessels
(Figs. 2 and 3) .
Patients in group 4 were also maintained continuously on low-dose
topical steroid medication (prednisolone acetate, 0.5%, once a day or
once every other day) after FND. In all 4 patients, the inflammation
began to resolve within 1 week, and the frequency of inflammatory
episodes was reduced. In one patient with herpes simplex viral
interstitial keratitis (with secondary glaucoma, controlled by
trabeculectomy), although the episodes of flare-up were reduced, a
small (<1 mm) well-circumscribed, circular area of thinning with
ectasia developed in the area of HSV keratitis scar after FND.
Four patients (two in group 1, one in group 2, and one in group 4)
required repeat FND once, and one patient (group 4) required repeat FND
twice, after 1 to 2 weeks, due to recanalization of the vessels
occluded or opening of collaterals, after the first treatment session.
The two patients in group 1 had deep vessels in two and three
quadrants, respectively. The patients in group 3 had recurrent graft
rejections associated with deep stromal vessels in two quadrants
approaching the host graft junction. Despite treatment with argon laser
and steroids, the vessels were still active. The rejection resolved
with regression of vessels after FND.
Of the 14 patients treated, occlusion of all vessels treated was
observed in 8 patients (57.1%); in 4 patients (28.5%) 75% of treated
vessels were occluded, and in 2 patients (14.2%) only 50% of the
treated vessels were occluded. Four of the latter 6 patients required
repeat treatment.
Corneal intrastromal hemorrhages were observed in three patients, which
cleared without any sequelae in two patients and in one left a fine
crystalline deposit that itself did eventually clear
(Figs. 2B 2C 2D) .
The advantages and disadvantages of corneal vascularization have
long been recognized. The need to treat corneal opacification,
recurrent immune-mediated inflammation, and reduced vision associated
with corneal vessels has always been felt, and various methods to
occlude vessels have been developed and used over the years.
Topical and periocular steroids have been popular, but the risks of
cataracts, glaucoma, and superinfection associated with the long-term
use of these drugs have been a limiting factor. Nonsteroidal
anti-inflammatory drugs and cyclosporin A were found to be largely
ineffective in controlling or limiting corneal
vascularization.
19 Other invasive and noninvasive methods
such as radiation,
7 thio-tepa,
8 cryotherapy,
9 and conjunctival recession have been found
to have limited clinical value.
Photocoagulation of vessels
10 11 12 13 14 15 16 17 20 has been shown to be
an effective alternative to the above methods. Cherry and
Garner
13 14 first reported the use of argon laser for the
treatment of corneal vessels in humans. In their study four patients
were treated, two with chemical burns and two with herpes simplex
keratitis. There were two failures, one success, and one partial
success. Marsh and coworkers
11 21 treated 41 lipid
keratopathy patients with corneal argon laser photocoagulation (CALP)
with a minimum follow-up period of 9 months. Twenty-eight of these
patients had a decrease in the extent or density of corneal opacity,
and 33 patients had improvement or no change in their vision. Nirankari
and Baer
18 treated 13 patients with CALP for deep stromal
vascularization. They reported good results with regard to reversal of
active graft rejection episodes and partial clearing of corneal
opacification after CALP.
Baer et al.
15 prospectively treated 25 eyes of 23 patients
with CALP using 577 nm yellow dye laser. They reported reversal of
graft rejection and a statistically significant reduction in area of
vascularization (reduction of 68% in the vascularized area). They also
achieved a significant reduction in the vascularized area, from 46.4%
to 27.3%, in nine patients treated for lipid keratopathy. In their
series laser photocoagulation was not found to be effective in patients
with extensive corneal neovascularization.
In our experience, CALP is of limited value because of its inevitable
complications of underlying iris atrophy and pupillary ectasia. The
risk of inadvertent retinal (or macular) photocoagulation, although
small, is of concern. We have found that laser ablation of corneal
efferent vessels (analogous to veins) is comparatively easy because
they are wider and have a relatively slower flow. Conversely, the
afferent vessels (analogous to arteries) are narrower, deeper, and have
a rapid pulsatile flow and are more difficult to ablate. Consequently,
recanalization of these vessels occurs in a high proportion of cases.
The technique of FND can be performed under topical anesthesia, is
simple, is inexpensive, and can be performed by any ophthalmic surgeon.
It can be applied at any depth to occlude both afferent and efferent
vessels with equal efficacy. When afferent and efferent vessels are
located close to each other, both can be occluded simultaneously, with
a single pass of the needle. This reduces intrastromal bleeding, which
is known to occur when the efferent vessel is occluded before the
afferent (as can occur with CALP). Although we have used a side-cutting
needle, which most corneal surgeons are familiar with, a round vascular
needle could be used instead. However, greater difficulty may be
encountered in passing a round-body needle into the desired plane of
the vessel to be occluded.
In our study, 14 patients with corneal vascularization were
prospectively treated with FND. In patients in group 3 (with graft
rejection reactions), successful reversal of rejection episodes was
achieved. In 3 patients CALP was attempted before FND. After CALP,
early apparent control of the rejection episode in all three patients
was followed by relapse. This was related to recanalization of some of
the vessels and also shunting of blood through collateral vessels.
Moreover, two of the three patients had accidental suture lysis as a
result of CALP. This is another important complication that has to be
anticipated while treating patients for this specific indication with
laser. The implications of this for grafts with running sutures is
significant. The success in the rejection group could be attributed to
inhibition of both afferent and efferent limbs of the immune response
by obliteration of both groups of vessels.
In group 2, both the patients had complete obliteration of vessels with
stabilization of corneal opacity and visual acuity. Because this group
had only two patients, no firm conclusions can be drawn, but these
results were comparable to Marsh’s studies of lipid keratopathy
patients.
11 12 21 The patients in group 1 had less
bleeding during trephination, and the grafts remained clear with no
rejection episodes until the last follow-up (9 months). However,
because these patients were considered high risk, in all four patients
a HLA class I matched (two or three alleles) donor was used, and in
three patients FK506 was used postoperatively. Therefore, the success
of the corneal transplant procedure with regard to absence of rejection
episodes cannot be attributed to FND of corneal vessels alone. Both HLA
class I matching and use of immunosuppressive agents are important in
preventing rejection episodes, and a randomized study controlling for
these variables will need to be done to assess the true worth of FND
alone in patients with this indication for vessel occlusion.
In the four patients with disciform keratitis (group 4), FND was
associated with resolution of active inflammation in three. Although
the clinical course of herpes stromal keratitis may wax or wane,
corneal clearing shortly followed FND.
We have found that deep vessels (active or quiescent) occupying two or
more quadrants or vessels arborizing in host graft junction needed to
be treated more than once. In such situations, although the major
vessels remained occluded, finer vessels in the vicinity of the
occluded vessels, which at the time appeared inconsequential, acted as
collaterals and established a new circulation. Persistence of active
stromal inflammation will induce further new vessel ingrowth. However,
in many instances, active stromal inflammation is potentiated by the
presence of vessels. FND of vessels helps to break this vicious cycle
and, together with other adjunctive treatment (e.g., steroid drops),
can facilitate the resolution of stromal inflammation.
There were few side effects observed with FND. Transient whitening of
the cornea was observed in the stroma immediately surrounding the
needle, at whatever depth it was placed. This occurred in all patients
treated with FND and persisted for 24 to 48 hours, with complete
resolution. No inadvertent corneal perforation with the needle occurred
in any of the patients.
Two conclusions can be drawn from this study: FND is a safe and
effective alternative treatment for occluding corneal vessels and
vessel occlusion has some beneficial effect on graft rejection and
before PK. However, this needs to be further evaluated by double-blind,
randomized, and controlled studies. Vessel occlusion appears to be a
useful adjunct to other treatment modalities in the management of graft
rejection episodes. The results obtained from the two patients of lipid
keratopathy treated in this study suggest that it may be of some value
in arresting the progress of this condition, but the regression of
deposited lipid is not accelerated by vessel occlusion. The value of
FND in preventing or reducing episodes of graft rejection (in high-risk
individuals) and episodes of immune-mediated corneal inflammation (in
herpes simplex viral keratitis and others) needs to be further
assessed.
Submitted for publication August 27, 1999; revised December 28, 1999; accepted January 7, 2000.
Commercial relationships policy: N.
Corresponding author: Harminder S. Dua, Department of Ophthalmology, B floor, South block, Nottingham University Hospital, Queens Medical Centre, Nottingham, NG7 2UH, UK.
harminder.dua@nottingham.ac.uk
Table 1. Demographics and Clinical Data
Table 1. Demographics and Clinical Data
| No. | Age | Eye | Diagnosis | Etiology | CNV QD | Depth | Activity | RX No. | Laser | Steroid | Pre-VA | Post-VA | Follow-Up | % of Vessel Closure |
| 1 | 60 | RE | Disciform scar | Herpes simplex | 2 | S, D, VD | Q | 2 | N | Y | 1/60 | 1/60 | 10 | 100% |
| 2 | 75 | LE | Disciform scar | Bacterial keratits | 3 | S, D, VD | Q | 2 | N | Y | 1/60 | 2/60 | 9 | 75% |
| 3 | 82 | RE | Disciform scar | Herpes zoster | 4 | S, D | Q | 1 | N | N | 2/60 | 2/60 | 9 | 50% |
| 4 | 65 | RE | Disciform scar | Herpes zoster | 1 | S, D | A | 1 | N | N | 6/9 | 6/9 | 12 | 50% |
| 5 | 70 | LE | Graft rejection | Corneal edema | 4 | S, VD, D | A | 1 | Y | N | HM | HM | 10 | 75% |
| 6 | 84 | RE | Graft rejection | Fuchs dystrophy | 1 | S, D | A | 1 | N | Y | 1/60 | 6/60 | 12 | 75% |
| 7 | 51 | LE | Graft rejection | Keratoconus | 2 | S, D | A | 2 | Y | Y | HM | HM | 6 | 100% |
| 8 | 70 | RE | Graft rejection | Corneal scar | 1 | D, VD | A | 1 | Y | Y | 6/60 | 6/24 | 15 | 100% |
| 9 | 12 | LE | Lipid keratopathy | Herpes zoster | 1 | S, D | Q | 1 | N | N | 6/60 | 6/60 | 12 | 100% |
| 10 | 23 | RE | Lipid keratopathy | Unknown | 1 | S, D | Q | 1 | N | N | 6/9 | 6/9 | 8 | 100% |
| 11 | 39 | LE | Pre-PK | Fuchs dystrophy | 4 | S, D | A | 1 | Y | N | 2/60 | 3/60 | 24 | 100% |
| 12 | 24 | LE | Pre-PK | Keratoconus | 4 | D | A | 3 | N | N | 6/18 | 6/18 | 9 | 100% |
| 13 | 65 | LE | Pre-PK | Herpes simplex | 2 | D, VD | A | 2 | N | N | CF | CF | 9 | 100% |
| 14 | 10 | RE | Pre-PK | Graft rejection | 3 | D | A | 2 | N | Y | 6/36 | 6/24 | 11 | 75% |
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