The anti-VEGF era of retinal treatments has been revolutionary to the field of ophthalmology. However, along with greater access to intravitreal injections, we have seen greater treatment burden in terms of increasing clinical volume and logistical considerations for patients. Multiple studies have also demonstrated that undertreatment in conditions like exudative AMD and diabetic macular edema (DME) can lead to limited improvements in vision.

The Port Delivery System (PDS) for ranibizumab (Genentech) aims to combat these issues through the implantation of a permanent intraocular reservoir that is refillable via an in-office procedure. The PDS provides a continuous delivery of a customized ranibizumab formation (100 mg/mL) over a 6-month period. The results of the ARCHWAY phase 3 clinical trial in patients with exudative AMD responsive to anti-VEGF therapy demonstrated noninferiority of PDS with 24-week dosing when compared to monthly ranibizumab injections. Additionally, 98% of patients in the PDS arm did not require any supplemental therapy during the first injection refill period. Currently, the PDS system is being investigated in the PAGODA phase 3 clinical trial in patients with DME.

The PDS surgical implantation and refill–exchange procedures for the ARCHWAY trial (248 patients in the PDS arm), while generally well tolerated, showed some unique adverse events. These included a vitreous hemorrhage rate of 5.2%, retinal detachment requiring surgery (2 cases), conjunctival bleb formation in 6.6% of patients, and conjunctival retraction/erosion in 4.4%. Endophthalmitis occurred in 4 patients, 3 of whom had conjunctival retraction associated with the infection.

These complications emphasize the necessity of precise and meticulous surgical technique for PDS implantation. In our center’s experience, close attention to every surgical step is crucial, with each serving as a foundation to the next. We present below our experiential surgical pearls that, in our opinion, lead to a higher rate of initial implantation success and a decreased occurrence of these adverse events.

THE RIGHT PATIENT

Patient selection is critical for PDS success. A careful assessment of the patient’s wet AMD pattern must be made. Is the patient a “frequent flyer” requiring monthly injections? Does the patient have trouble with transport or other logistical factors creating difficulty in arriving for their appointments or a need for less frequent follow-up? Is the patient healthy enough for surgery? These considerations can help determine which patients may be more suitable candidates for PDS.

LOOK BEFORE YOU LEAP

A preoperative examination is necessary to help determine tissue integrity. Undertake a careful examination of the conjunctiva, particularly superotemporally (ST), for previous incisional procedures, scarring, or any physical anomaly causing decreased conjunctival mobility, which can impede proper conjunctival flap replacement over the PDS and lead to long-term conjunctival retraction. Scleral tissue strength is crucial to maintaining a tight apposition of the implant to the scleral wall. Any form of scleral ectasia should be carefully accounted for. A patient’s propensity for retinal detachment should also be determined preoperatively, as the presence of a PDS implant may make placing a scleral buckle technically more difficult. Consider in glaucoma patients whether the ST quadrant may be needed for future surgical procedures.

MIND THE CONJUNCTIVA AND TAKE CARE WITH TENON

Conjunctival and Tenon placement over the PDS implant is crucial for long-term infection control and PDS integrity. The conjunctiva should be handled thoughtfully and delicately with the finesse of a glaucoma surgeon. Nontoothed forceps should be used at all times to avoid button-hole formation. Identification and careful undermining of both the conjunctiva and the Tenon tissue is necessary to decrease tension over the implant.

KEEP CALM AND CAUTERIZE

Hemostasis is a crucial step for successful PDS implantation. Controlling bleeding not only allows for a more precise scleral incision, but also greatly lowers the risk of postoperative vitreous hemorrhage. Cautery is key for hemostatis in certain steps. Wet-field cautery is the preferred tool to achieve control over the episcleral vasculature prior to scleral incision. Gentle application is necessary, as over-cauterizing the sclera can lead to scleral shrinkage or delayed scleral melt. Care should be taken to preserve limbal stem cells to avoid corneal epithelial issues in the future.

CUT ONCE, CUT RIGHT

Proper conjunctival peritomy creation is perhaps the most important determinant of long-term implant success. Starting the peritomy right at the limbus is crucial, because a more posterior peritomy will lead to future conjunctival retraction. A properly placed perilimbal followed by radial incision should give about a 6 mm x 6 mm conjunctival peritomy. The incisions should have smooth edges without buttonholes to ensure proper coverage without tension over the implant upon incision closure.

THE RIGHT KIND OF TENSION

Placement of a suture through the superotemporal cornea provides exposure as well as necessary countertraction. This is important during the various incision times because it reduces the force needed for forceps stabilization. This traction suture also provides the force needed to keep the lips of the scleral incision open during pars plana lasering to prevent scleral lasering and incision expansion.

INCISION PRECISION

The key to long-term implant stability and ease of refilling procedure is tight apposition of the PDS to the walls of the scleral incision. The incision must be 3.5 mm in length. We recommend using a fixed caliper with clear markings and wiping off the excessive ink to create precise incision guide points. Single gentle decisive incisions are key during the creation of scleral openings It is crucial to maintain a single vertical plane (no tunneling) with the blade to ensure a tight fit for the implant and decrease the risk of vitreous hemorrhage. Do not grab the lip of the incision for stability or traction as this will delaminate the incision lip, leading to future ectasia and PDS displacement. If the incision is longer than 3.5 mm, use a suture to shorten it on one end. It is absolutely critical that the length of the incision (internal and external) does not exceed 3.5 mm because incisions longer than 3.5 mm have been shown to enlarge over time. We recommend erring on the side of shorter with the initial incision, because there is a tendency for the incision to expand during application of laser to the pars plana at the incision edges. The use of an incision gauge is crucial, and the gauge must be placed into the incision instead of hovering over it for an accurate measurement.

PATIENCE WITH LASERING

Applying laser to the pars plana for hemostasis is needed for controlled entry into the vitreous cavity. As mentioned above, the scleral incision tends to expand after laser, so it is crucial to not apply laser directly to the wound lip for size control. Carefully drying the choroid during lasering leads to better uptake and visualization. We recommend having an assistant frequently dab the incision between laser burns with a Weck-Cel (BVI) sponge to achieve this. Great care must be taken not to perforate the choroid early with the sponge. The laser burn is of a long duration (1 second), so it is crucial to keep your foot on the pedal until the burn is complete. Stay on single-shot mode to increase control. Expect to see smoking and graying of the pars plana. It is important to be patient and not to proceed with painting strokes, as there is a chance for scleral involvement. Continue lasering until you see a perforated appearance or splitting of the pars plana. It is normal to see a small dome of vitreous coming through the pars plana opening. This can be vitrectomized before or after implant insertion depending on the prolapsed amount. Vitrectomy should be performed using a cutter as opposed to scissors and sponge, because pulling on prolapsed vitreous can lead to retinal detachment.

CLOSE WITH CARE

Ensuring conjunctival and Tenon closure in the absence of tension is necessary for long-term PDS integrity. If tension is noted on the conjunctival tissue while reopposing, do not hesitate to undermine the conjunctiva and Tenon tissue more posteriorly to create freedom of movement. It is important to avoid radial passes during placement of the apex anchor suture, which should pass from outside the incision to the inner edge, with the needle oriented parallel to the limbus. Use of a 8-0 Vicryl suture on a noncutting vascular needle, such as a BV needle, can help avoid conjunctival trauma. It is necessary to ensure Tenon tissue is also captured with each needle pass. At the end of the closure, the conjunctiva must be taut and nonretractable at the limbus. If retraction can be easily induced, then a mattress suture at the limbus is necessary.

CONCLUSION

The PDS implant adds to our arsenal of long-term management options for patients with VEGF-driven processes. However, it is important to understand the underlying surgical technique and proceed with finesse to achieve long-term success. With careful patient selection and planning, the PDS can largely mitigate treatment burden for years to come. RP