Ocular Cryotherapy

Ocular cryotherapy is the therapeutic use of cold temperatures to treat disorders of the lids or eyes. Cryotherapy has been used in ophthalmology since the mid-1960s. With the exception of cataract extraction, ocular cryotherapy is generally used as a surface technique, with the probe being applied to the lids or eye without any incision into the tissue. Because of the absence of an incision, it is considered to be a less invasive type of procedure than incisional surgery.

Medical use of cryotherapy is based on the tissue changes induced by subfreezing temperatures. Living tissue responds to extremely cold temperatures through ice formation, both within cells and also in the extra cellular fluid surrounding cells. In addition, subfreezing temperatures cause ice formation within small blood vessels, interrupting blood supply to adjacent cells. A combination of these factors destroys living tissue through ischemia and necrosis and induce inflammation as a response to cell death.[1]

There are many applications of cryosurgery in the field of ophthalmology; the most significant of these are summarized below. The only significant contraindications are active infection (bacterial, viral, or fungal) of the ocular surface or eyelids and lack of cooperation on the part of the patient.

Cryoextraction of cataracts was the first well-accepted use of ocular cryotherapy. During the 1950s and 1960s, cataract surgery was performed through a 10-12 mm incision with the cataractous lens being removed totally. The lens was grasped with a capsule forceps or a suction device. Lens breakage was common because of the delicacy of the lens capsule (the outer covering of the lens). In the mid 1960s, a cryoprobe was first used for lens extraction. During the 1970s, this became the most widely used method of cataract extraction.

Retinal cryopexy continues to be used as a means of repairing retinal breaks (holes or tears), which have long been recognized to be the cause of most retinal detachments. Application of cold to the choroid and retinal pigment epithelium yields cell death and subsequent scarring, resulting in sealing of the edges of retinal breaks.

Retinal cryopexy is also widely used during scleral buckling procedures for retinal detachment and pneumatic retinopexies for retinal detachment.[2] It is sometimes performed at the time of pars plana vitrectomy to induce chorioretinal adhesions, though it has largely been replaced by endolaser techniques in this setting.

Other applications of cryotherapy in ophthalmology include the following:

• Cyclocryopexy for advanced glaucoma – In severe intractable glaucoma that is not amenable to conventional glaucoma medication or surgery, ocular cryopexy applied to the ciliary body through a transscleral application can reduce aqueous production, thereby lowering intraocular pressure

• Peripheral retinal cryoablation for neovascular glaucoma – Destruction of the peripheral retina by means of cryotherapy can cause iris neovascularization to recede in neovascular glaucoma

• Retinal cryoablation for retinopathy of prematurity (ROP) – In multicenter prospective clinical trials, destruction of the peripheral retina in premature infants with ROP slows disease progression and improves the chance of maintenance of vision; ocular cryotherapy has markedly altered the prognosis of ROP

• Retinal cryoablation for peripheral uveitis (intermediate uveitis or pars planitis) – Destruction of the far peripheral retina can reduce peripheral uveitis and cause improvement in macular edema secondary to peripheral uveitis

• Transconjunctival cryotherapy for retinal toxoplasmosis – Active toxoplasmic lesions in the peripheral retina can be treated with transconjunctival cryotherapy; Toxoplasma gondii organisms are destroyed by extreme cold

• Retinal cryoablation for Coats disease - This most likely basis for this use a decrease in production of vascular endothelial growth factor (VEGF) by the peripheral retina and a subsequent decrease in vascular proliferation[3]

• Peripheral retinal cryoablation to induce regression of proliferative diabetic retinopathy – Although this approach has been used successfully, it has largely been supplanted by panretinal photocoagulation with an argon laser, which has greater efficacy[4, 5, 6]

• Transconjunctival cryopexy for larva migrans of the eye – The intraocular nematode in this condition (Toxocara canis or Toxocara cati) can be destroyed by transconjunctival cryopexy if it is located away from the posterior retina

• Peripheral cryoablation of the retina and choroid for retinal vasculitis of various etiologies

• Cryoablation of malignant peripheral melanomas of the choroid or ciliary body – This allows salvage of vision and the eye in selected cases

• Cryoablation of retinoblastomas – Peripheral retinoblastomas can be successfully treated with transconjunctival or transscleral cryopexy

• Cryoablation of metastatic lesions to the choroid. These secondary malignancies (most commonly from the breast or lung) can be destroyed with cryosurgery if their location is peripheral enough

• Cryosurgery for conjunctival neoplasias of the epithelium – This can be considered as an alternative to surgical excision

• Cryotherapy for malignancies of the lids (eg, basal cell carcinomas)

• Freezing of lash roots for recurrent trichiasis

Cryotherapy requires a substance that is extremely cold (ie, a cryogen) and a delivery system by which the cold can be brought into contact with the target tissue. Commonly used cryogens include liquid nitrogen, which has a boiling temperature of –196°C; carbon dioxide snow, which has a boiling temperature of –79°C; and liquid argon or Freon, which has a boiling temperature of –35°C. These substances can be applied to tissue either with an aerosol spray or with a cryoprobe.

A cryoprobe is a closed system where the cryogen is circulated within a metal probe and the cold probe is applied to the tissue. Specifically, the probe is supplied with a cryogen (eg, liquid nitrogen) from a pressurized source. Liquid nitrogen converts to gaseous nitrogen within the probe, cooling the probe to extremely low temperatures.

The probe is made of 3 long concentric tubes. The inner tube serves as a conduit for liquid nitrogen flow to the tip of the probe. The space between the inner tube and the middle tube serves as a path for the return of gaseous nitrogen from the tip. The tip of the probe is a chamber into which the liquid nitrogen flows from the inner tube and from which the gaseous nitrogen returns through the space between the inner and middle tubes. Freezing takes place in the tissue around the chamber on the tip of the probe.

The amount and rate of tissue destruction are related to the temperature of the cryogen, the size of the cryoprobe, the circulation to the tissue involved, the type of tissue being treated, and the duration of the cryogen application. Cryotherapy has both immediate and delayed effects on tissue.

The freezing propagates from the tip of the probe outward into tissue. The cells near the probe surface will be cooled more rapidly and to lower temperatures than those farther away from the probe. The cells at different locations in the frozen tissue will be at different temperatures for various periods of time as a function of their distance from the probe surface, the cooling fluid employed, the shape of the cryosurgical probes, and the type of tissue frozen.

Equipment used in cryotherapy includes the following:

• Cryoconsole

• Appropriately sized cryoprobe for the procedure – The cryoprobe connects to the cryoconsole with insulated tubing that is part of the probe itself; probes with varying tip sizes and angulations have been developed for different applications; generally, the larger the probe tip is, the colder it will become

• Source of electricity to run the cryoconsole

• Tank of gas, usually carbon dioxide, that is attached through valves and tubing to the cryoconsole

• In all retinal cases, an indirect ophthalmoscope and condensing lens

In addition to a substance that is extremely cold (ie, a cryogen), cryotherapy requires a delivery system by which the cold can be brought into contact with the target tissue. Cryogens can be applied to tissue either with an aerosol spray or with a cryoprobe (connected to a cryoconsole, which in turn is connected to a gas tank and an electricity source).

A cryoprobe is a closed system where the cryogen is circulated within a metal probe and the cold probe is applied to the tissue. Specifically, the probe is supplied with a cryogen (eg, liquid nitrogen) from a pressurized source. Liquid nitrogen converts to gaseous nitrogen within the probe, cooling the probe to extremely low temperatures.

The cryoprobe connects to a cryoconsole with insulated tubing that is part of the probe itself. Probes with varying tip sizes and angulations have been developed for different applications; generally, the larger the probe tip is, the colder it will become.

Anesthesia

Topical anesthesia using proparacaine drops is adequate for most cases of retinal cryopexy. Local infiltration of lidocaine is used in cryotherapy for conjunctival neoplasms, lid neoplasms and trichiasis.

Retrobulbar or peribulbar anesthesia is used in cryoablation of choroidal tumors (melanomas or metastatic tumors), peripheral cryoablation of the retina or choroid, cryotherapy for ocular toxoplasmosis or Coats disease, and cyclocryotherapy for neovascular glaucoma.

General anesthesia is used in cryotherapy for retinopathy of prematurity and retinoblastoma.

Positioning

Most ocular cryotherapy procedures are performed with the patient in a recumbent position on a narrow table so that the surgeon can approach the patient from the head of the table or from either side.

Make sure that there is adequate gas in the tank and that connections have been correctly made and tightened. The appropriate cryoprobe for the task must be used (see Equipment). Before beginning, make sure that the cryotherapy equipment is functioning correctly by depressing the foot switch and observing proper cooling of the tip.

If an incision will be required in the planned procedure, surgical preparation and draping are necessary. If no incision will be required, sterile techniques are not necessary.

After the appropriate anesthesia has been instituted (see Patient Preparation), the cryoprobe is applied while still warm to the tissue undergoing treatment. The footswitch is then depressed to allow coolant to flow to the tip. An ice ball should form at the tissue at the tip. Once tissue has started adhering to the tip, the probe should not be moved, because of the risk of tearing or breaking the tissue.

For cryoextraction of cataracts, after the cataract incision is made, the surface of the lens is dried and a room-temperature cryoprobe tip applied to the lens capsule. The cryogen is then released into the tip, causing the tip to cool rapidly and adhere to the lens capsule. Once adhesion is complete, the lens can be removed by pulling gently on the cryoprobe.

For retinal cryopexy, the probe is applied to the conjunctiva while the surgeon looks inside the eye with an indirect ophthalmoscope and gently presses on the probe. The pressure from the probe can be seen as an indentation in the retina. When the probe is in the correct position relative to the retinal break, the cryogen is released into the probe, and the retina can be seen to whiten as it freezes. Retinal swelling can be observed after the probe is removed, and scarring develops within about 1 week.

Complications of cryotherapy include the following:

• Overfreezing – Because cryotherapy causes tissue destruction, application of excessively cold temperatures or excessive duration of cryoapplication can damage normal tissue; the amount and duration of cryotherapy must be appropriate for the desired purpose

• Underfreezing – Application of cryotherapy without achieving appropriately low tissue temperatures will not yield the desired results

• Freezing nontarget tissue – This can occur if the cryoprobe is inadvertently applied to adjacent tissue that was not supposed to be treated

• Tissue cracking – This can occur if the probe is moved after it has adhered to the tissue; the probe should be allowed to defrost completely before an attempt is made to remove it from the tissue