A 44-year-old man with type 2 diabetes mellitus diagnosed approximately 1 year earlier presented with a history of previous focal photocoagulation in both eyes (performed approximately 2 months earlier). Best-corrected VA was 20/200 in both eyes. Fundus photography showed diffuse diabetic macular edema and vascular sheathing in the right eye (Fig. 1A) and diffuse diabetic macular edema with cotton-wool spots in the left eye (Fig. 1B). Early-frame fluorescein angiography of the right eye revealed a widened foveal avascular zone; Fig. 2A). Mid-frame fluorescein angiography of the left eye showed a widened foveal avascular zone and early diffuse dye leakage (Fig. 2B). Late-frame fluorescein angiography revealed diffuse dye leakage in both eyes (Fig. 2C, right eye; Fig. 2D, left eye). Optical coherence tomography (OCT) showed diffuse macular thickening (right eye: 473 microns with cystoid spaces and submacular fluid, Fig. 3A; left eye: central macular thickness of 303 microns, Fig. 3B).
Figure 1. (A) Fundus Photograph of the Right Eye in Case #1, Showing Diffuse Diabetic Macular Edema and Vascular Sheathing. (B) Fundus Photograph of the Left Eye Illustrating Diffuse Diabetic Macular Edema and Cotton-Wool Spots.
Figure 2. (A) Early-Frame Fluorescein Angiogram of the Right Eye in Case #1, Showing a Widened Foveal Avascular Zone. (B) Mid-Frame Fluorescein Angiogram of the Left Eye, Indicating a Widened Foveal Avascular Zone as Well as Early Diffuse Dye Leakage. (C and D) Late-Frame Fluorescein Angiograms of the Right Eye and Left Eye Respectively, Revealing Diffuse Dye Leakage.
Figure 3. (A) Optical Coherence Tomography (OCT) of the Right Eye in Case #1, Showing Diffuse Macular Thickening of 473 Microns with Cystoid Spaces and Submacular Fluid. (B) OCT of the Left Eye also Shows Diffuse Macular Thickening, with a Central Macular Thickness of 303 Microns.
After obtaining appropriate informed consent, the patient was treated with IVTA (Kenalog, Bristol-Myers Squibb, New York, NY) 4 mg in 0.1 mL, in both eyes.
At 3 months post-injection, VA improved to 20/80 in the right eye, but remained 20/200 in the left eye. OCT demonstrated improvement in macular thickening in both eyes (in the right eye: improvement from 473 microns to 207 microns, Fig. 4A; in the left eye: improvement from 303 microns to 190 microns, Fig. 4B).
Figure 4. (A) OCT of the Right Eye in Case #1 at 3 Months Following IVTA Injection (4 mg in 0.1 mL), Showing Improvement in Macular Thickening, from 473 Microns to 207 Microns. (B) OCT of the Left Eye at 3 Months Following IVTA Injection, Showing Improvement in Macular Thickening from 303 Microns to 190 Microns.
Following continued observation, at 5 months post-injection, VA improved to 20/60 in the right eye, but remained 20/200 in the left eye. Intraocular pressure (IOP) was elevated in both eyes (25 mm Hg in the right eye, 38 mm Hg in the left eye). The patient was treated with latanoprost 0.005% (Xalatan; Pfizer Inc., New York, NY) in both eyes at bedtime to reduce IOP.
Six weeks later (about 7 months post-injection), VA declined to 20/100 in the right eye, but improved to 20/100 in the left eye. Fundus photography (Figs. 5A and 5B) demonstrated improvement in macular edema in both eyes; in the right eye also exhibited some improvement in vascular sheathing, inferiorly in particular (Fig. 5A). OCT demonstrated recurrent macular thickening in the right eye (change from 207 microns to 333 microns, Fig. 6A), but essentially stable macular thickness in the left eye (change from 190 microns to 189 microns, Fig. 6B). IOP was 15 mm Hg in the right eye and 35 mm Hg in the left eye.
Figure 5. (A) Fundus Photograph of the Right Eye in Case #1 at 7 Months Post Injection, Showing Improvement in Macular Edema with Some Improvement in Vascular Sheathing as Well, Particularly Inferiorly. (B) Fundus Photograph of the Left Eye, Showing Improvement in Macular Edema and Prior Photocoagulation Spots.
Figure 6. (A) OCT of the Right Eye in Case #1 at 7 Months Post IVTA Injection. Note Mild Recurrence of Macular Edema from 207 Microns to 333 Microns. (B) OCT of the Left Eye, Indicating that the Macular Thickness Was Essentially Stable at 189 Microns.
Because of the increase in IOP following IVTA, in the right eye was treated with off-label intravitreal bevacizumab (0.125 mg in 0.1 mL; Avastin; Genentech, Inc., San Francisco, CA). The left eye was not injected but was treated with timolol/dorzolamide (Cosopt; Merck & Co., Inc., Whitehouse Station, NJ) twice daily, and eventually brimonidine (Alphagan P; Allergan, Inc., Irvine, CA) 3 times daily as well.
The patient has been followed for over 3 years and has required intermittent retreatment with bevacizumab. VA stabilized in the 20/70 range in both eyes and the patient was eventually able to discontinue all topical glaucoma medications. The patient went on to develop a visually significant cataract in the left eye and underwent cataract surgery about 16 months following IVTA treatment.
A 61-year-old woman with type 1 diabetes mellitus since age 27 presented with a history of treated proliferative diabetic retinopathy, status post panretinal photocoagulation (PRP) in both eyes, and status post pars plana vitrectomy in the left eye for nonclearing vitreous hemorrhage. At the time of presentation, this patient had diffuse diabetic macular edema in both eyes unresponsive to previous intravitreal bevacizumab in both eyes, and VA was 20/60 in both eyes. Fundus photography showed PRP and diabetic macular edema, but the images are technically suboptimal because of a small pupil and moderate nuclear sclerotic cataract, and they are not shown here. OCT revealed macular thickening (in the right eye: 629 microns, Fig. 7A; in the left eye: 739 microns, Fig. 7B) and submacular fluid.
Figure 7. (A) OCT of the Right Eye in Case #2, Showing a Central Macular Thickness of 629 Microns. (B) OCT of the Left Eye, Showing that the Central Macular Thickness Was 739 Microns Prior to IVTA.
After appropriate informed consent, both eyes were treated with IVTA (Kenalog, Bristol-Myers Squibb, New York, NY) 4 mg in 0.1 mL.
After 3 months, VA had improved to 20/40 in the right eye and 20/30 in the left eye. IOP remained within normal limits. OCT revealed improvement in macular thickening in both eyes (in the right eye: from 629 microns to 299 microns, Fig. 8A; in the left eye: from 739 microns to 340 microns, Fig. 8B). After 6 months, VA had declined to 20/60 in both eyes and recurrent diabetic macular edema was noted. Both eyes were retreated with IVTA (4 mg in 0.1 mL). The macular edema improved, but the patient developed progressive posterior subcapsular cataract in both eyes and underwent bilateral cataract surgery.
Figure 8. (A) OCT of the Right Eye in Case #2 at 3 Months Post Injection, Showing Improvement in Macular Thickening from 629 Microns to 299 Microns. (B) OCT of the Left Eye, Showing that the Macular Thickening Was Reduced from 739 Microns to 340 Microns at 3 Months After IVTA Injection.
A 74-year-old woman with a history of non-insulin dependent diabetes mellitus for 17 years and an intra-ocular lens implant in the right eye for 4 years, presented with decreased vision and bilateral clinically significant macular edema. At the time of the presentation, bilateral focal laser photocoagulation was carried out.
The patient returned four months later with worsened visual acuity at 20/70 in each eye with bilateral persistent diabetic macular edema; OCT showed macular thickening of 493 microns in the right eye and 496 microns in the left eye (Fig. 9). High-dose (20 mg) preservative-free IVTA was injected in both eyes followed by repeat focal laser photocoagulation in both eyes. Four months later, the visual acuity remained stable at 20/70+ in the right eye and improved to 20/40 in the left eye; OCT showed improvement of macular thickening to 344 microns in the right eye and 259 microns in the left eye (Fig. 10). Intraocular pressure was 21 mm Hg in the right eye and 25 mm Hg in the left eye, and brimonidine 0.15% (Alphagan P; Allergan, Irvine, CA) in each eye twice a day was added, which decreased the IOP below 20 and maintained the normalized pressure.
Figure 9. Case #3, Note Macular Thickening of 493 Microns in the Right Eye and 496 Microns in the Left Eye.
Figure 10. Case #3, Four Months After IVTA Injections, Note Improvement of Macular Thickening to 344 Microns in the Right Eye and 259 Microns in the Left Eye.
Nine months after the high-dose preservative-free IVTA injections, her right eye had declined to 20/200 while the left continued to improve to 20/30. OCT central retinal thickness was 416 microns in the right eye and 239 microns in the left eye, and IOP was 18 mm Hg in the right eye and 21 mm Hg in the left eye with brimonidine 0.15% twice a day in each eye. She was scheduled for further focal laser photocoagulation for her right eye (Fig. 11).
Figure 11. Case #3, Nine Months After IVTA Injections, Note Recurrent Macular Thickening in the Right Eye (416 Microns) but Stable Anatomy in the Left Eye (239 Microns).