Journal of Ophthalmology

Review Article

Off-Label Use of 0.19 mg Fluocinolone Acetonide Intravitreal Implant: A Systematic Review

Table 1

Main characteristics of the included studies.


Disease		Author and year	Type of study	Number of subjects	Number of eyes	Follow-up	Conclusions

Radiation-induced maculopathy		Zimmerman et al. [26], Germany	Case series (peer-reviewed)	5 (37–68 years)	5: 4 pseudophakic and 1 phakic	2–8 months	5 patients presented a decrease in foveal thickness. 4 patients improved their retinal structures and visual acuity. Adverse events: 1 patient presented IOP elevation (required medical therapy).
Paraneoplastic syndromes	MAR	Karatsai et al. [20], United Kingdom	Case report (peer-reviewed)	1 (73 years old)	2: 2 phakic	36 months	BCVA left eye: from 20/40 to 20/20. BCVA right eye: from 20/80 to 20/20. ERG with retinal function improvement in both eyes (1 year after in the right eye and 2 years after in the left eye). Adverse events: both eyes developed cataracts 2 years after, requiring cataract surgery.
Paraneoplastic syndromes	CAR	Abdulla and Taylor [27]	Retrospective (not peer-reviewed)	6	11 eyes: (7 treated with FAc implant and 4 treated with IVIg)	6 months	FAc implant outcomes: BCVA improved; MD improved; IOP dropped; color vision improved; did not require multiple treatments or multiple hospital admissions. FAc implant adverse events: One eye from the FAc implant group underwent cataract surgery. IVIg outcomes: BCVA declined; MD improved; IOP increased; color vision improved; did require multiple treatments or hospital admission.
Sjogren’s syndrome-related keratopathy		Wasielica-Poslednik et al. [21], Germany	Case report (peer-reviewed)	1 (52 years old)	2 eyes (left eye was treated with FAc implant and the right eye served as a control)	6 months	FAc implant outcomes: BCVA improved from hand motion to 16/100; No more surgical interventions were needed; No alteration in IOP was documented. Control eye: 2 PKPs, 1 vitrectomy, 5 AMTs, and 3 tarsorrhaphies because of recurrent keratolysis and perforations.
Retinal vein occlusion		Coelho et al. [22], Portugal	Case report (peer-reviewed)	1 (65 years old)	1:—1 pseudophakic	12 months	BCVA improved from 20/100 to 20/25. Central foveal thickness decreased from 578 μm to 393 μm. After 12 months, there was still some edema on the OCT. IOP maintained normal, controlled by medication.
Cystoid macular edema	After vitrectomy	Ong et al. [23], USA	Case report (peer-reviewed)	1 (79-year-old)	2:—2 pseudophakic	11–13 months	BCVA left eye: from 20/80 to 20/40. BCVA right eye: from 20/64 to 20/50. Both with anatomical improvement on OCT. IOP remained normal.
	Retinal detachment repair	Alfaqawi et al. [24], United Kingdom	Case report (peer-reviewed)	1 (65 year-old)	1	20 months	BCVA improved from 6/36 to 6/18. Anatomically, presented dry fovea. Adverse events: Anterior uveitis during the first week after surgery and elevated IOP, which was controlled with medication for 4 weeks.
	Disrupted anterior-posterior segment border (FLAT)	Herold et al. [25], Germany	Case report (peer-reviewed)	2	2	1 month	BCVA improved one line in one patient and stayed the same in the other >10% reduction of central retinal thickness on OCT in both patients. Adverse events: Subjective discomfort in the suture area that resolved during the first 4 weeks.
Diabetic retinal neurodegeneration		Lynch et al. [28], USA	Retrospective (peer-reviewed)	130 (mean age 69.6 years)	160:—110 pseudophakic - 38 phakic—12 not recorded	Mean follow-up post FAc implant: 13.2 months	Region 1: The rate of inner retinal loss was not statistically significant. Region 2: The rate of inner retinal loss was statistically significant. The rate of thinning went from 4.0 μm/y to 1.1 μm/y after FAc implant treatment.
Retinitis pigmentosa	Photoreceptor neuroprotection	Glybina et al. [29], USA	RCT (peer-reviewed)	32 RCS rats	64	4 weeks	ERG: ERG a- and b- wave amplitudes were preserved in all animals receiving FAc implants. There was an 80% reduction in the control groups. This preservation in the FAc implant groups was statistically significant compared to control groups. Retinal histology: ONL thickness was greater than in the control groups. INL thickness was not different between groups. Microglial cell count: FAc significantly reduced the overall number of microglial cells in the photoreceptor cell layer, when compared to the control groups. The number of activated microglial cells was also reduced. Adverse events: No cataract formation, no inflammatory changes, or retinal detachment. IOP showed no statistically significant differences between groups. Overall conclusion: The 0.2 μm/d FAc implant was reproducibly more effective than the higher dose implant.
Retinitis pigmentosa	Retinal degeneration	Glybina et al. [30], USA	RCT (peer-reviewed)	32 S334ter-4 rats	64	8 weeks	ERG: ERG a-wave amplitudes did not change significantly in the 0.2 μm/d group. ERG b-wave amplitudes were greater in the FAc groups than in the control groups. These observations indicate that steroid treatment was associated with the preservation of rod-driven electrical activity during phototransduction. Retinal histology: The 0.2 μm/d FAc implant group presented a thicker ONL. INL thickness was not significantly different between groups. Microglial cell count: Microglial cell count was significantly lower in both FAc implant groups when compared to the control groups. Adverse events: No signs of infection, inflammation, media opacities, or IOP were observed during the 8-week postoperative period in any animal. Overall conclusion: The 0.2 μm/d FAc implant was reproducibly more effective than the higher dose implant.