Patient 1

A 72-year-old woman with a history of non-neovascular AMD and a best-corrected Snellen visual acuity of 20/60 in the right eye and 20/30 in the left eye underwent bilateral intravitreal injection of autologous adipose tissue–derived stem cells for the treatment of non-neovascular AMD. The patient underwent the procedure at a stem-cell clinic that had an institutional review board–approved research trial (NCT02024269) listed on ClinicalTrials.gov at the time; however, the written information provided to the patient did not mention participation in a clinical trial, review or approval by an institutional review board, or an association with a trial listed on ClinicalTrials.gov.

The patient reported that she had found the stem-cell clinic through its listing on ClinicalTrials.gov. She also reported that she was under the impression that she was participating in a clinical trial and that she had met the criteria of the trial. She paid $5,000 for the bilateral procedure. The consent form indicated the risk of blindness.

Figure 1. Figure 1. Findings on Ophthalmologic Examination in Patient 1. In Panel A, a high-resolution ultrasonographic image shows anterior subluxation of the lens of both eyes, more prominently in the left eye. In Panel B, a posterior segment ultrasonographic image shows moderately dense, mobile vitreous opacities with macular thickening in both eyes and possible retinal detachment and vitreoretinal adhesions in the left eye. In Panel C, fundus photographs of both eyes show diffuse intraretinal hemorrhage. The view is hazy in the left eye because of corneal edema. In Panel D, an optical coherence tomographic image of the right eye shows macular thickening without cystoid macular edema. The thickening is more prominent in the inner retina (arrow). In Panel E, a fluorescein angiogram of the right eye shows blockage from the hemorrhages (arrows), a window defect in the temporal macula, and an area of staining in the temporal periphery. No vasculitis was seen. Fluorescein angiography of the left eye could not be performed because of severe corneal edema.

The patient presented to the Bascom Palmer Eye Institute in Miami 3 days after the intravitreal injection. On presentation, her visual acuity was perception of hand motion in both eyes, and the intraocular pressure was 66 mm Hg in the right eye and 59 mm Hg in the left eye. Examination of the anterior segment showed conjunctival injection, corneal microcystic edema, fixed, mid-dilated pupils, and peripheral iridocorneal touch in both eyes. The nuclear sclerotic cataract was anteriorly displaced in both eyes, as shown by high-resolution ultrasonography (Figure 1A). The patient had a dense vitreous hemorrhage in both eyes, which obscured the view of the posterior pole. Posterior segment ultrasonography showed mildly to moderately dense, mobile, vitreous opacities with macular thickening in both eyes and possible retinal detachment and vitreoretinal adhesions in the left eye (Figure 1B).

Because of the anterior displacement of the crystalline lens and elevated intraocular pressure in both eyes, bilateral pars plana vitrectomies and lensectomies were performed. Histologic examination showed histiocytes and no malignant cells. After removal of the dense vitreous hemorrhage, diffuse intraretinal hemorrhage was identified in both eyes (Figure 1C). A localized rhegmatogenous retinal detachment that was identified in the right eye was managed with endolaser barricade of the tear and silicone oil tamponade. Silicone oil tamponade was chosen for tamponade in all patients during repair of retinal detachment because it facilitates visual rehabilitation and travel better than does air or gas tamponade, which greatly limits vision and precludes flight in commercial aircraft. Postoperative optical coherence tomography (OCT) revealed retinal thickening without cystoid macular edema in the right eye (Figure 1D). Fluorescein angiography of the right eye showed blockage from the hemorrhages and a temporal macula window defect, but it did not show changes consistent with vasculitis (Figure 1E). OCT and fluorescein angiography could not be performed in the left eye because of corneal edema.

Over time, both of the patient’s retinas became markedly atrophic. One year after the vitrectomies and lensectomies, her right retina was detached, with severe proliferative vitreoretinopathy, and she had no light perception in both eyes because of atrophy. Her intraocular pressure was controlled with topical medications for glaucoma.

Patient 2

Quiescent neovascular AMD was diagnosed in a 78-year-old woman with a best-corrected Snellen visual acuity of 20/50 in the right eye and 20/100 in the left eye after she received bilateral injections of anti–vascular endothelial growth factor (VEGF) drugs in both eyes over the course of 2 years and before she received bilateral intravitreal injections of autologous adipose tissue–derived stem cells at the same stem-cell clinic mentioned previously. Like Patient 1, she was aware of the clinical trial posted on ClinicalTrials.gov by the stem-cell clinic. She also paid $5,000 for the same procedure that Patient 1 had undergone.

Figure 2. Figure 2. Findings on Ophthalmologic Examination in Patients 2 and 3. In Panel A, fundus photographs of both eyes in Patient 2 show intraretinal hemorrhage and vitreous hemorrhages. In Panel B, an optical coherence tomographic (OCT) image shows macular thickening without cystoid macular edema and an epiretinal membrane in the right eye and retinal thickening without cystoid macular edema and geographic atrophy in the left eye in Patient 2. An old scar caused by laser retinopexy is visible in the superotemporal quadrant of the right eye (arrow). In Panel C, a fluorescein angiogram shows blockage from the hemorrhages, areas of staining temporally, and a window defect in the central macula in both eyes in Patient 2. No vasculitis was seen. In Panel D, montage fundus photographs of both eyes in Patient 2 show bilateral attached retinas with peripheral laser chorioretinal scars. In Panel E, fundus photographs of both eyes in Patient 3 show severe combined tractional and rhegmatogenous retinal detachment with proliferative vitreoretinopathy in the right eye and geographic atrophy in the left. An old scar caused by cryopexy is visible in the superotemporal quadrant of the left eye (arrow). In Panel F, an OCT image of the left eye in Patient 3 shows geographic atrophy.

Approximately 2 days after Patient 2 received bilateral intravitreal injections, she presented to both the Bascom Palmer Eye Institute and to the Center for Sight in Sarasota, Florida. On presentation, her visual acuity was such that she could count fingers with both eyes, and the intraocular pressure was 13 mm Hg in both eyes. Examination of the anterior segment of each eye showed conjunctival injection and grade 1+ anterior chamber cells in both eyes. The patient had bilateral vitreous hemorrhages and diffuse intraretinal and preretinal hemorrhages (Figure 2A). OCT showed an epiretinal membrane with fundus thickening without cystoid macular edema in the right eye and geographic atrophy and fundus thickening without cystoid macular edema in the left eye (Figure 2B). Fluorescein angiography showed blockage from the hemorrhages, but it did not show vasculitis (Figure 2C). She underwent serial observation, but 16 days after the injection, a combined tractional and rhegmatogenous retinal detachment with proliferative vitreoretinopathy developed in the right eye and was treated with scleral buckle, pars plana vitrectomy, membrane peel, and silicone oil tamponade. Consistent with zonular weakness, there was anterior dislocation of the patient’s intraocular lens and lens capsule during the fluid–air exchange intraoperatively.

Thirty-eight days after the patient received the bilateral intravitreal injections, a combined tractional and rhegmatogenous retinal detachment with proliferative vitreoretinopathy developed in the left eye, which was treated with pars plana vitrectomy and silicone oil. Postoperatively, the patient’s retinas were attached after 1 year (Figure 2D), and her vision was perception of hand motion in the right eye and 20/200 in the left eye.

Patient 3

An 88-year-old woman with a visual acuity of 20/40 in the right eye and 20/200 in the left eye had a history of non-neovascular AMD with bilateral geographic atrophy and a retinal tear treated with cryopexy in the left eye 30 years before she received bilateral intravitreal stem-cell injections, as described in Patients 1 and 2. Patient 3 received injections at the same stem-cell clinic for $5,000.

Patient 3 presented 1 week after the procedure to the Dean McGee Eye Institute, Oklahoma City. On presentation, the patient’s visual acuity was light perception in the right eye and 20/200 in the left eye, and her intraocular pressure was 12 mm Hg in the right eye and 16 mm Hg in the left eye. She had an afferent pupillary defect in the right eye. Examination of the anterior segment of each eye was clinically significant for pseudophakia in both eyes. The patient had a total retinal detachment with proliferative vitreoretinopathy in the right eye and geographic atrophy with a superotemporal cryopexy scar in the left eye (Figure 2E). OCT imaging of the left eye showed geographic atrophy (Figure 2F). OCT imaging of the right eye was not performed.

The patient’s right eye was managed with a scleral buckle, pars plana vitrectomy, membrane peel, peripheral localized retinectomy, and silicone oil tamponade. Four weeks after the injection, a total retinal detachment with proliferative vitreoretinopathy developed in the patient’s left eye. Of note, during the intraoperative fluid–air exchange, there was anterior dislocation of the patient’s intraocular lens and lens capsule in both eyes consistent with zonular weakness. One year after surgery, the patient’s retinas were attached, and her visual acuity was perception of hand motion in the right eye and light perception in the left.