TNF-α Inhibitors for the Management of Intractable Corneal Melt: Report of Three Cases and Review of the Literature.

OBJECTIVE: To report three consecutive cases with noninfectious corneal melting, whose disease progression could only be halted with tumor necrosis-α (TNF-α) inhibitor infusion, with a review of the relevant literature. MATERIALS AND METHODS: Patients with toxic epidermal necrolysis, severe alkaline burn, and Sjögren syndrome had experienced severe corneal melting following penetrating keratoplasty, Boston type 1 keratoprosthesis implantation or spontaneously, respectively. Topical autologous serum eye-drops, medroxyprogesterone, and acetylcysteine formulations; frequent nonpreserved lubrication; systemic tetracyclines and vitamin-C supplements; topical and systemic steroids and steroid-sparing agents; surgical approaches including amniotic membrane transplantation, tectonic graft surgery; and tarsorraphy failed to alter the disease courses. RESULTS: Upon consultation with the rheumatology clinic, TNF-α inhibitor infliximab (Remicade; Centocor Ortho Biotech Inc, Horsham, PA) 5 mg/kg infusion was planned for each patient. After 0-, 2-, and 6-week doses, monthly infusion at the same dose was maintained for 12 months because of severe and intractable course of their diseases. Each case showed dramatic improvements in corneal melts; and sterile vitritis in the eye with Boston keratoprosthesis responded, as well. CONCLUSIONS: Inhibiting TNF-α-mediated expression of matrix metalloproteinases responsible for collagen breakdown should be considered in refractory cases, as a means of globe salvage.

A cross-sectional optical coherence tomography study in patients on taxane-based therapy and a case report with the literature review.

PURPOSE: To evaluate the characteristics of macular retinal and subfoveal choroidal changes in patients already on taxane-based therapy by the help of spectral domain optical coherence tomograpy (SD-OCT) and determine the incidence of taxane- related cystoid macular edema (CME). MATERIALS AND METHODS: In this cross-sectional case-control study, 202 patients who received taxane-based therapy due to treatment of various cancer and age and sex-matched 200 healthy control subjects were examined. Only patients who received at least 4 cycles of taxane-based therapy were taken into consideration for the taxane group. Taxane-based therapy was further divided into two subgroups; paclitaxel group (149 patients) and docetaxel group (53 patients). Central macular thickness (CMT) and central subfoveal choroidal thickness (CCT) were measured just once during their ongoing chemotherapy using SD-OCT and enhanced-depth imaging (EDI) OCT by Heidelberg OCT by a single examiner. RESULTS: Patients received a median of 7 cycles (range, 4-26) of paclitaxel or docetaxel and received a total cumulative dose of 852.81 ± 368.82 mg/m2 (range, 300-2310 mg/m2). Though the mean CMT was significantly thicker in the taxane group (224.9 ± 28.4 µm) than the healthy control group (215.9 ± 19.7 µm), there was no statistically significant difference between the paclitaxel (225.3 ± 28.2 µm) and docetaxel (224.2 ± 20.1 µm) groups. On the other hand, the CCT was not statistically significant different between the taxane versus control eyes and paclitaxel versus docetaxel patients. Taxane-related CME was detected only in one patient on paclitaxel. Overall, incidence of taxane-related maculopathy was 0.5% (1/202) of all patients in the taxane group. CONCLUSION: In our group of taxane receiving patients, incidence of taxane-related CME was 0.5%. In light of our study, we believe that clinicians should be alert on the occurence of taxane-related CME and carefully scrutinize the patients whenever any suspicion is arisen.

Corneal recovery in a rabbit limbal stem cell deficiency model by autologous grafts of tertiary outgrowths from cultivated limbal biopsy explants.

PURPOSE: To determine the corneal regenerative capacity of sequentially generated primary, secondary, and tertiary limbal explant outgrowths in a limbal stem cell deficiency (LSCD) surgical model. METHODS: Two-millimeter-long limbal shallow biopsies were surgically excised from the upper quadrant of the right eye of rabbits and set on preserved amniotic membrane for explant culture. After the generation of primary outgrowth, the biopsies were sequentially transferred to new amniotic membrane to generate secondary and then tertiary outgrowths. Eighteen rabbits were subjected to a 360° limbal peritomy extending into the scleral zone and combined with superficial keratectomy of the corneal periphery and thorough mechanical debridement of the central cornea in their left eye. Right eye outgrowths, six of each generation, were engrafted on the ocular surface. Clinical outcomes (neovascularization, corneal clarity, and corneal fluorescein staining) were graded after 6 months. Post-mortem corneas were compared with histology, immunochemistry for p63 and Krt3, ABCG2-dependent dye exclusion, and capacity for outgrowths in explant culture. RESULTS: Immunohistology and western blot of the outgrowths for p63 and Krt3 indicated no differences in expression between the primary and tertiary outgrowths for these two markers of growth and differentiation. Clinically, all rabbits treated with amniotic membrane alone developed severe LSCD. Most rabbits grafted with cell outgrowths from all three outgrowth generations achieved stable (>6 months) recovery of the ocular surface. There were partial failures of grafts performed with two secondary and tertiary outgrowths. However, Kruskal-Wallis statistical analysis of the clinical scores yielded no significant difference between the three groups (p=0.524). Histology showed full anatomic recovery of grafts made with primary and tertiary outgrowths. Krt3 and p63 expression throughout the whole limbal corneal epithelium with primary or tertiary outgrowths was not distinguishable from each other. The percentage of dye-excluding cells present within this zone and the capacity of the explant epithelial outgrowth of the regenerated peripheral corneal zone were also on par with those of the donor corneas. The Krt3-negative cells that characterize the basal epithelial layer of the normal limbus could not be found in any regenerated cornea from the primary to tertiary outgrowths. CONCLUSIONS: Our results demonstrate that in rabbits post-primary explant outgrowths retain the capacity for LSCD recovery found in primary explants.

A 5-year study of adenoviruses causing conjunctivitis in Izmir, Turkey.

Adenoviruses are a common cause of conjunctivitis. Genotypes are diverse and differ according to population and geographical distribution of the virus. There is limited data regarding ocular adenoviral infections and genotype distribution in Turkey. This study aimed to determine the adenovirus genotypes and their epidemiological features among patients with conjunctivitis between 2006 and 2010, in Izmir, Turkey. Adenoviral DNA was detected by PCR in 213 of 488 (44%) of the ocular samples collected from patients with viral conjunctivitis during the 5-year study period. Of these, 101 (47%) were randomly chosen and genotyped by sequence analysis. Seven genotypes were identified, including 3, 4, 8, 11, 19, 37, and 53. Genotype 8 and 4 were the dominant types detected in 67 (66.3%) and 25 (24.7%) of the samples, respectively. Other five genotypes (3, 11, 19, 37, 53) were detected in 9 (8.9%) samples. Genotype and seasonal differences observed throughout the study. Human adenoviruse (HAdV)-8 was the most frequent type, except 2008. The prevalence of genotype 4 increased starting from 2006, became dominant in 2008 and decreased in the following years. The peak season was mostly spring months, although it was possible to detect positive samples throughout the year. In conclusion, genotype 8 followed by genotype 4 was the most frequent adenoviral types causing conjunctivitis during the 5-year study period. Findings suggest that there is a slow shift between genotypes throughout the years.

Erdafitinib-Induced Bilateral Multifocal Serous Retinal Detachments and Severe Dry Eye Related Unilateral Peripheral Ulcerative Keratitis in a Patient with Metastatic Urothelial Carcinoma.

Background: A case of bilateral multifocal serous retinal detachments and dry eye complicated with unilateral peripheral ulcerative keratitis (PUK) during erdafitinib therapy is described. Case description: A 76-year-old male underwent a baseline examination two months after initiating 8 mg erdafitinib therapy (April 2023) due to metastatic urothelial carcinoma. Left subfoveal serous retinal detachment was observed initially but the treatment was resumed as he was asymptomatic. In May 2023, bilateral multifocal subretinal fluid pockets were identified, and the patient was still asymptomatic. However, in June 2023 he complained of bilateral redness and a stinging sensation in his right eye. Bilateral severe dry eye and right PUK were diagnosed. He was prescribed dexamethasone eye drops and sodium hyaluronate artificial tears for both eyes. One week later corneal staining decreased, and progression of PUK ceased. Erdafitinib therapy was discontinued in June 2023 due to the planned transurethral prostatectomy. By July 2023, after discontinuation of the drug and administration of the topical treatment, the dry eye improved and the PUK became inactive. There was also resolution of subretinal fluid pockets in the right eye and a reduction of subretinal fluid pockets in the left eye. After the reinitiation of erdafitinib therapy, serous retinal detachments recurred in both eyes in September 2023, but both corneas remained stable with topical low-dose dexamethasone, cyclosporine-A and artificial tear usage. Conclusion: Erdafitinib therapy may lead to concurrent anterior and posterior segment complications. Multidisciplinary monitoring is crucial for patients undergoing erdafitinib therapy to prevent possible visual disturbances. LEARNING POINTS: Erdafitinib, a tyrosine kinase inhibitor of fibroblast growth factor receptors 1 to 4, is administered for the treatment of locally advanced, unresectable or metastatic urothelial carcinoma but however is fraught with several systemic and ocular side effects.Concurrent anterior and posterior segment ocular involvement could be encountered in patients undergoing erdafitinib therapy.Maintaining a high level of suspicion and closely monitoring for potential ocular complications through collaborative efforts is essential for all patients undergoing erdafitinib therapy.

Necrotic arachnidism of the eyelid due to Loxosceles rufescens spider bite.

A 69-year-old woman was awakened with redness and swelling of the left upper eyelid a few days before her presentation. She also noticed a dead spider on her bed. Ophthalmic examination revealed severe left periorbital hyperemia, edema and a wide necrotic area on the upper eyelid. Systemic condition of the patient was well. She was hospitalized with the diagnosis of necrotic arachnidism of the left upper eyelid. Systemic corticosteroid and antibiotic treatment was commenced. No surgical intervention was carried out. A week later, whole upper eyelid was covered with a black eschar. This black eschar shrank with time, and it detached completely within 8 weeks and the lesion healed without a disfiguring scar. Meanwhile, the offending spider was identified as Loxosceles rufescens. Although rare, eyelid may be a biting site for Loxosceles spiders and a favorable result may be obtained with conservative management.

Identification of Acanthamoeba genotype T4 and Paravahlkampfia sp. from two clinical samples.

In this study, two free-living amoebae strains, Acanthamoeba genotype T4 and Paravahlkampfia sp., which were isolated from keratitis cases are presented. While the Acanthamoeba strain was isolated as a single agent, the Paravahlkampfia strain was found together with herpes simplex virus. Neither of the patients were contact lens wearers, but they did have a history of minor corneal trauma. Amoebae were detected on non-nutrient agar covered with Escherichia coli. Based on PCR-amplified 18S rRNA-gene analysis the first isolate was identified as Acanthamoeba genotype T4 and the second as Paravahlkampfia sp. In thermotolerance tests, the maximum temperature at which trophozoites continued to divide was determined as 37 degrees C for this Acanthamoeba strain and 35 degrees C for the Paravahlkampfia strain. To the best of our knowledge, the Acanthamoeba strain described herein is the second molecularly identified Acanthamoeba strain in an Acanthamoeba keratitis patient in Turkey. However, the Paravahlkampfia isolate is believed to be the first strain that has been isolated from a keratitis patient and has been molecularly differentiated from Vahlkampfia.

Effect of diode laser cyclophotocoagulation on the anterior segment: an Orbscan Study.

PURPOSE: To evaluate the effect of transscleral contact diode laser cyclophotocoagulation (TCDLC) on corneal topography, central corneal thickness (CCT), and anterior-chamber depth (ACD). METHODS: The Orbscan II system was used to determine the changes in corneal topography, CCT, and ACD before and after TCDLC in 25 eyes of 24 patients. RESULTS: Mean prelaser astigmatism was 4.51 +/- 1.81, 4.64 +/- 3.47, and 5.40 +/- 3.04 D at central and 3- and 5-mm zones, respectively. Mean postlaser astigmatism was 4.54 +/- 2.59, 4.75 +/- 3.33, and 5.57 +/- 3.12 D at central and 3- and 5-mm zones at 10 days and 3.99 +/- 2.01, 4.05 +/- 2.20, 5.52 +/- 4.60 D at 1 month, respectively, showing no statistically significant difference. Prelaser CCT was 540.72 +/- 103.48 microm. Postlaser CCT was 617.08 +/- 86.35 microm at 10 days and 569.88 +/- 70.36 microm at 1 month. CCT was significantly thicker at 10 days compared with prelaser CCT, whereas CCT at 1 month was not statistically different. ACD showed a nonsignificant decrease after TCDLC from 3.77 +/- 0.81 to 3.38 +/- 0.85 mm at 10 days and 3.58 +/- 0.78 mm at 1 month. CONCLUSIONS: TCDLC does not alter corneal topography or ACD significantly. However, CCT increases during the 10 days after TCDLC and returns to normal at 1 month, which might be related to the inflammation induced by cyclophotocoagulation. Increased CCT may lead to artificially high intraocular pressure measurements within the first 4 weeks after surgery.

Conjunctival involvement in chronic recurrent multifocal osteomyelitis.

PURPOSE: To report a case of chronic recurrent multifocal osteomyelitis (CRMO) with conjunctival involvement. METHODS: Retrospective chart review. RESULTS: A 10-year-old girl who complained of fatigue and debilitating pain in both hips and legs for >1 year had recurrent episodes of redness and discharge in both eyes with little response to different topical medications. The diagnosis of CRMO was confirmed with the help of magnetic resonance imaging, bone scan, and bone biopsy results. She had moderate hyperemia and multiple discrete salmon-colored lesions in both palpebral and fornical conjunctivae. Biopsy revealed chronic inflammatory infiltration composed predominantly of lymphocytes forming a follicular pattern. Conjunctival lesions worsened during relapses of skeletal symptoms, improved during remission, and resolved shortly after the initiation of oral prednisolone therapy. No recurrence was observed during 16 months of follow-up. CONCLUSIONS: Salmon-colored conjunctival lesions may accompany CRMO and respond favorably to systemic steroid therapy.

Acute vitreomacular traction syndrome after uneventful phacoemulsification.

We prospectively evaluated 59 eyes following uneventful phacoemulsification and intraocular lens implantation with optic coherence tomography at one and seven postoperative days (POD). Acute vitreomacular traction was observed in two eyes (3.3%) at the first POD. Spontaneous resolution occurred in both eyes within one week. The temporary visual loss associated with acute vitreomacular traction syndrome may go unnoticed as visual acuity rapidly improves.

Unilateral acute retinal necrosis initially presenting with painful orbitopathy.

Painful orbital inflammation and scleritis-like clinical appearance can be the initial manifestation of acute retinal necrosis. We report a 25-year-old woman who first presented with painful orbitopathy that eventually developed into unilateral acute retinal necrosis with typical fundus appearance. Our case illustrates the importance of careful fundus examination in cases presenting with painful orbital inflammation.

The effect of various alpha1-adrenergic receptor antagonists on pupillary dilation.

We prospectively evaluated the effect of various systemic alpha1 adrenergic receptor antagonists on pupillary dilation in patients with benign prostatic hyperplasia. Patients who are at risk for intraoperative floppy iris syndrome cannot be elucidated simply by judging preoperative dilation.

Comparison of culture media indicates a role for autologous serum in enhancing phenotypic preservation of rabbit limbal stem cells in explant culture.

In this study, we aimed to compare the effects of six different cell culture media and autologous serum (AS) on the phenotypic characteristics of rabbit limbal epithelial stem cells (LESC) cultivated on porous polyethylene terephthalate (PET) membranes. Limbal explants from rabbit corneas were grown on PET membrane inserts in five different media: DMEM-F12 with fetal bovine serum (FBS) (DMEM-F12-FBS), with pluripotin (DMEM-F12-pluripotin) and with autologous serum (DMEM-F12-AS), Epilife, Keratinocyte Serum Free Medium (KSFM) and Defined-Keratinocyte Serum Free Medium. The effects of different media were evaluated by total cell yield from explants, measuring the expression of proteins by immunofluorescence and gene expression by Real Time PCR. In all five media tested, most of the limbal epithelial cells (LEC) which proliferated from explants were positive for cytokeratin (CK) 14 (85-90%), indicating that all five media support the growth of LESC from explants. The expression of differentiation markers; CK 3 and 12 was highest in DMEM-F12-FBS (56%), was lower in Epilife and KSFM (26 and 19%, respectively), with the lowest values (13%) obtained in DMEM-F12-AS. Gene expression of limbal cultures on PET membrane inserts was compared to fresh limbal tissue. In DMEM-F12-FBS, DMEM-F12-pluripotin, and DMEM-F12-AS, expression of potential LESC markers CXCR4 and polycomb complex protein BMI-1 were similar to limbal tissue. DMEM-F12 with 10% AS maintained a higher percentage of potential stem cell marker genes and lower expression of genes involved in differentiation compared to Epilife or KSFM. Our study shows that rabbit LEC can be cultivated on PET inserts using DMEM-F12 with autologous serum without a requirement for amniotic membrane or feeder cells.

Interaction with intraocular lens materials: does heavy silicone oil act like silicone oil?

PURPOSE: To determine the interaction of heavy silicone oil with various intraocular lens (IOL) materials and whether heavy silicone oil covers the silicone IOL optic as silicone oil does. SETTING: Department of Ophthalmology, Dokuz Eylul University, Izmir, Turkey. METHODS: The study group comprised 5 poly(methyl methacrylate) (PMMA) IOLs, 4 foldable silicone IOLs, 5 foldable hydrophilic acrylic IOLs, and 5 foldable hydrophobic acrylic IOLs. Each IOL was bathed in balanced salt solution (BSS) for 10 minutes and then placed in heavy silicone oil dyed with Sudan Black for another 10 minutes. Afterward, each IOL was reimmersed in BSS for 5 minutes and examined under the light microscope. Digital images were analyzed to determine the optic area covered with heavy silicone oil. RESULTS: The mean heavy silicone oil coverage was 7.05% +/- 7.88% (SD) (range 1.13% to 20.54%) on PMMA IOLs, 100% on silicone IOLs, 12.17% +/- 11.43% (range 1.25% to 31.52%) on hydrophobic acrylic IOLs, and 34.64% +/- 13.28% (range 12.57% to 44.42%) on hydrophilic acrylic IOLs. Heavy silicone oil coverage of silicone IOLs was statistically significantly greater than the coverage of other IOL materials. CONCLUSION: Heavy silicone oil acted the same as silicone oil and covered the entire surface of silicone IOLs.

Topical steroids in the management of Churg-Strauss syndrome involving the conjunctiva.

PURPOSE: To discuss a case of Churg-Strauss syndrome that developed bilateral conjunctival involvement while recovering from miliary tuberculosis. METHODS: Case report and literature review. RESULTS: A 22-year-old man who was on oral prednisolone for Churg-Strauss syndrome since 2002 contracted miliary tuberculosis in June 2004. The diagnosis was confirmed by liver biopsy. Ophthalmologic examination was within reference limits except for bilateral multifocal choroiditis. A combined therapy of rifampicin, ethambutol, streptomycin, and morphazinamide was started on June 24, 2004. Complete recovery was achieved, and the antituberculosis therapy was terminated in June 2005. The patient noted redness and pain in both eyes a month later. He had bilateral irregular, pink-yellow, gravel-like infiltrations involving the bulbar conjunctiva. Biopsy revealed granulomas with central fibrinoid necrosis, histiocytes, and eosinophils, suggestive of conjunctival involvement of Churg-Strauss syndrome. Topical dexamethasone 0.1% drops were started 4 times per day and tapered gradually. Lesions totally regressed within 2 months. No recurrence was noted during a follow-up of 11 months. CONCLUSIONS: Churg-Strauss syndrome may rarely involve the conjunctiva, and conjunctival lesions respond favorably to topical steroids.

Unilateral Adult Xanthogranulomatous Infiltration of the Conjunctiva, Limbus and Sclera Leading to a Combined Ophthalmic Artery and Central Retinal Vein Occlusion.

OBJECTIVE: To describe the features of a female patient with a biopsy-proven xanthogranulomatous infiltration of the conjunctiva, limbus and sclera who had an exudative retinal detachment, combined ophthalmic artery and central retinal vein occlusion unilaterally. METHOD: A-53-year old otherwise healthy woman presenting with a painful visual loss in her right eye underwent an ophthalmic examination, meticulous systemic work-up and histopathologic assessment. RESULTS: Ophthalmic examination revealed multiple subconjunctival masses, upper limbal infiltrations, trace cells in the anterior chamber, pale looking posterior fundus, 360 degree scattered retinal hemorrhages and marked exudative retinal detachment in her right eye. Left eye was completely normal.A biopsy taken from one of the subconjunctival masses demonstrated a diffuse infiltration of the histiocytes and this was interpreted as a xanthogranulomatous infiltration with the help of immunohistochemical staining techniques. CONCLUSION: Present case is the only reported adult case with xanthogranulomatous-like infiltration of the eyeball featuring both anterior and posterior segment involvement without any concomitant major systemic disturbances.

The effect of scleral buckling surgery on corneal astigmatism, corneal thickness, and anterior chamber depth.

PURPOSE: To evaluate the effect of scleral buckling surgery on corneal topography, corneal thickness, and anterior chamber depth. METHODS: Thirty-two eyes of 32 patients who underwent encircling buckling surgery for rhegmatogenous retinal detachment were included in the study. Fellow eyes comprised the control group. Orbscan II topography system was used to determine the changes in corneal topography, corneal thickness, and anterior chamber depth before surgery and 1 week, 1 month, and 3 months after surgery. Statistical analyses used in the study were independent t test, paired t test, one way analysis of variance, and correlation analyses. RESULTS: Postoperatively, mean central corneal astigmatism at 1 week, 1 month, and 3 months was 4.3 +/- 2.0 diopters (D), 3.3 +/- 1.6 D, and 3.1 +/- 1.0 D, respectively. The change between 1 week and 3 months was statistically significant. Central cornea was thickened at the first postoperative week. The thickness gradually decreased to the preoperative levels at 3 months. Anterior chamber depth decreased, and the anterior chamber remained shallow after the surgery. The comparison between preoperative (2.94 +/- 0.6 mm) and postoperative anterior chamber depth was statistically significant at 1 week (2.57 +/- 0.7 mm), 1 month (2.83 +/- 0.7 mm), and 3 months (2.73 +/- 0.6 mm). CONCLUSIONS: Corneal changes after scleral buckling surgery were mild to moderate and the cornea almost resumed its preoperative parameters in 3 months' time. However, the anterior chamber remained shallow during 3 months of follow-up.

Intraocular lens haptic fracturing with the neodymium:YAG laser In vitro study.

PURPOSE: To determine the neodymium:YAG (Nd:YAG) laser energy threshold to fracture the haptic of various currently marketed intraocular lenses. SETTING: Dokuz Eylul University, Ophthalmology Department, Izmir, Turkey. METHODS: Four haptic materials-poly(methyl methacrylate) (PMMA), hydrophobic acrylic, hydrophilic acrylic, and polyvinylidene fluoride-were tested. The intraocular lenses (IOLs) were grouped according to haptic material. Each group comprised 9 IOLs. Beginning laser energy was 4 mJ. If no crack was noted, energy was increased by 0.5 mJ at every 20 shots and the procedure continued until a fracture was noted. If the fracture could not be developed despite reaching an energy level of 10 mJ, the procedure was terminated. Statistical analysis was performed to determine the differences within groups. RESULTS: Hydrophobic acrylic and polyvinylidene fluoride haptics required higher energy and more laser shots to create a fracture than hydrophilic acrylic and PMMA haptics. CONCLUSIONS: Neodymium:YAG laser haptic fracturing can be a viable option to cut the fibrosed haptic before explanting any IOL. It was demonstrated in vitro that it is easier to fracture hydrophilic acrylic and PMMA haptics than hydrophobic acrylic and polyvinylidene fluoride haptics.

Nodular Scleritis in Association with Panuveitis in Behçet's Disease.

This case report involves a 32-year-old man with Behçet's disease who had simultaneous bilateral anterior uveitis, unilateral nodular scleritis, and occlusive vasculitis with retinal hemorrhages. Although scleritis is not a classical feature of Behçet's disease, a diagnosis of Behçet's disease should be considered in patients with scleritis.

The Effect of Intravitreal Azithromycin on the Albino Newborn Rabbit Retina.

PURPOSE: To evaluate the effect of intravitreal azithromycin on the retina in a newborn rabbit model. METHODS: Twelve, two-week old New Zealand albino rabbits were divided into two groups (six in each). The right eyes of six rabbits received 0.75 mg (0.05 mL) azithromycin and the right eyes of the remaining six rabbits 1.5 mg (0.1 mL) azithromycin intravitreally. Left eyes were served as the control and received the same volume of saline. All eyes were enucleated at the third postinjection week. Retinal histology was examined by light microscopy. Apoptosis of the retinal cells was further evaluated by immunohistochemical staining for caspase-3 and in situ terminal deoxynucleotidyl transferase-mediated biotin-deoxyuridine triphosphate nick-end labeling (TUNEL) of DNA fragments. RESULTS: Light microscopy demonstrated no retinal abnormalities in all eyes. However, retinal nuclear DNA fragmentation was evident in both study groups (33.6% with 1.5 mg and 21.4% with 0.75 mg azithromycin) with the TUNEL method. TUNEL staining ratio was statistically higher only in the second group treated with 1.5 mg azithromycin when compared to the control group (p=0.01 Mann Whitney U test). The ratio of caspase-3 positive cells in the two study groups was 21.5% and 20.2%, respectively. Caspase-3 staining ratio was statistically higher in both study groups when compared to the control eyes (p=0.00, p=0.00 respectively). The difference of TUNEL staining ratio between the two study groups was statistically significant (p=0.028), but there were no statistically significant differences in the two study groups by caspase-3 staining (p=0.247). CONCLUSION: In newborn rabbits, intravitreal azithromycin injection resulted in an apoptotic activity in the photoreceptor, bipolar and ganglion cells. Immunohistochemical analysis suggested that doses of 0.75 mg and 1.5 mg azithromycin, administered intravitreally might be toxic to the newborn rabbit retina.